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Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF‐β3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF‐β3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross‐sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF‐β3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF‐β3, pro‐inflammatory and anti‐inflammatory markers. A subset of patients were administered topical TGF‐β3 in order to evaluate its therapeutic effects. The expression pattern of TGF‐β3 was found to be stage‐dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF‐β3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF‐β3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF‐β3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF‐β3, which functions as an anti‐inflammatory and pro‐inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common digestive tract tumor with a high incidence and a poor prognosis. Traditional chemotherapy drugs are usually accompanied by unpleasant side effects, highlighting the importance of exploring new adjunctive drugs. In this study, we aimed to explore the role of ursolic acid (UA) in CRC cells. Specifically, HT‐29 cells were treated with UA at different concentrations (10, 20, 30, and 40 μM), and the expression of miR‐140‐5p, tumor growth factor‐β3 (TGF‐β3), β‐catenin, and cyclin D1 was determined by real‐time quantitative PCR. The cell cycle and apoptosis were checked by flow cytometry, and cell proliferation was detected by Cell Counting Kit‐8 assay. The HT‐29 cell model was established through overexpression (miR‐140‐5p mimics) and interference (miR‐140‐5p inhibitor) of miR‐140‐5p. Western blot was used to detect the protein expression of TGF‐β3. We found that UA could inhibit the proliferation of HT‐29 cells, block cells in the G1 phase, and promote cell apoptosis. After UA treatment, the expression of miR‐140‐5p increased and TGF‐β3 decreased. Notably, miR‐140‐5p downregulated the expression of TGF‐β3, while the overexpression of miR‐140‐5p exerted a similar function to UA in HT‐29 cells. Additionally, the messenger RNA expression of TGF‐β3, β‐catenin, and cyclin D1 was decreased in HT‐29 cells after UA treatment. In conclusion, UA inhibited CRC cell proliferation and cell cycle and promoted apoptosis by regulating the miR‐140‐5p/TGF‐β3 axis, which may be related to the inhibition of Wnt/β‐catenin signaling pathway. Highlights: Ursolic acid inhibits cell proliferation and promotes cell apoptosis and cell cycle arrest of colorectal cancer HT‐29 cells.Ursolic acid increased the expression of miR‐140‐5p.miR‐140‐5p exerts a similar function to ursolic acid by downregulating the expression of tumor growth factor‐‐β3 and inhibiting the Wnt/β‐catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives T peripheral helper (Tph) cells have major roles in pathological processes in SLE. We sought to clarify the mechanisms of Tph cell differentiation and their relevance to clinical features in patients with SLE. Method Phenotypes and functions of Tph cell-related markers in human CD4+ T cells purified from volunteers or patients were analysed using flow cytometry and quantitative PCR. Renal biopsy specimens from patients with LN were probed by multicolour immunofluorescence staining. Results Among multiple cytokines, transforming growth factor (TGF)-β3 characteristically induced programmed cell death protein 1 (PD-1)hi musculoaponeurotic fibrosarcoma (MAF)+, IL-21+IL-10+ Tph-like cells with a marked upregulation of related genes including PDCD-1, MAF, SOX4 and CXCL13. The induction of Tph-like cells by TGF-β3 was suppressed by the neutralization of TGF-β type II receptor (TGF-βR2). TGF-β3-induced Tph-like cells efficiently promoted the differentiation of class-switch memory B cells into plasmocytes, resulting in enhanced antibody production. The proportion of Tph cells in the peripheral blood was significantly increased in patients with SLE than in healthy volunteers in concordance with disease activity and severity of organ manifestations such as LN. TGF-β3 was strongly expressed on macrophages, which was associated with the accumulation of CD4+ C-X-C chemokine receptor (CXCR5)-PD-1+ Tph cells, in the renal tissue of patients with active LN. Conclusion The induction of Tph-like cells by TGF-β3 mainly produced from tissue macrophages plays a pivotal role in the pathological processes of active LN by enhancing B-cell differentiation in patients with SLE. [ABSTRACT FROM AUTHOR]

Background: Achilles tendon (AT) midsubstance injuries may heal suboptimally, especially in athletes. Transforming growth factor–beta 3 (TGF-β3) shows promise because of its recently discovered tendinogenic effects. Using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) may enhance the results by a sustained-release effect. Hypothesis: The application of TGF-β3 will enhance AT midsubstance healing, and the NP form will achieve better outcomes. Study Design: Controlled laboratory study. Methods: A total of 80 rats underwent unilateral AT transection and were divided into 4 groups: (1) control (C); (2) empty chitosan film (Ch); (3) chitosan film containing free TGF-β3 (ChT); and (4) chitosan film containing TGF-β3–loaded NPs (ChN). The animals were sacrificed at 3 and 6 weeks. Tendons were evaluated for morphology (length and cross-sectional area [CSA]), biomechanics (maximum load, stress, stiffness, and elastic modulus), histology, immunohistochemical quantification (types I and III collagen [COL1 and COL3]), and gene expression (COL1A1, COL3A1, scleraxis, and tenomodulin). Results: Morphologically, at 3 weeks, ChT (15 ± 2.7 mm) and ChN (15.6 ± 1.6 mm) were shorter than C (17.6 ± 1.8 mm) (P =.019 and =.004, respectively). At 6 weeks, the mean CSA of ChN (10.4 ± 1.9 mm2) was similar to that of intact tendons (6.4 ± 1.1 mm2) (P =.230), while the other groups were larger. Biomechanically, at 3 weeks, ChT (42.8 ± 4.9 N) had a higher maximum load than C (27 ± 9.1 N; P =.004) and Ch (29.2 ± 5.7 N; P =.005). At 6 weeks, ChN (26.9 ± 3.9 MPa) had similar maximum stress when compared with intact tendons (34.1 ± 7.8 MPa) (P =.121); the other groups were significantly lower. Histologically, at 6 weeks, the mean Movin score of ChN (4.5 ± 1.5) was lower than that of ChT (6.3 ± 1.8). Immunohistochemically, ChN had higher COL3 (1.469 ± 0.514) at 3 weeks and lower COL1 (1.129 ± 0.368) at 6 weeks. COL1A1 gene expression was higher in ChT and ChN at 3 weeks, but COL3A1 gene expression was higher in ChN. Conclusion: The application of TGF-β3 had a positive effect on AT midsubstance healing, and the sustained-release NP form improved the outcomes, more specifically accelerating the remodeling process. Clinical Relevance: This study demonstrated the effectiveness of TGF-β3 on tendon healing on a rat model, which is an important step toward clinical use. The novel method of using PLGA-b-PEG NPs as a drug-delivery system with sustained-release properties had promising results. [ABSTRACT FROM AUTHOR]

Background: Organogenesis from tonsil-derived mesenchymal cells (TMSCs) has been reported, wherein tenogenic markers are expressed depending on the chemical stimulation during tenogenesis. However, there are insufficient studies on the mechanical strain stimulation for tenogenic cell differentiation of TMSCs, although these cells possess advantages as a cell source for generating tendinous tissue. The purpose of this study was to investigate the effects of mechanical strain and transforming growth factor-beta 3 (TGF-β3) on the tenogenic differentiation of TMSCs and evaluate the expression of tendon-related genes and extracellular matrix (ECM) components, such as collagen. Results: mRNA expression of tenogenic genes was significantly higher when the mechanical strain was applied than under static conditions. Moreover, mRNA expression of tenogenic genes was significantly higher with TGF-β3 treatment than without. mRNA expression of osteogenic and chondrogenic genes was not significantly different among different mechanical strain intensities. In cells without TGF-β3 treatment, double-stranded DNA concentration decreased, while the amount of normalized collagen increased as the intensity of mechanical strain increased. Conclusions: Mechanical strain and TGF-β3 have significant effects on TMSC differentiation into tenocytes. Mechanical strain stimulates the differentiation of TMSCs, particularly into tenocytes, and cell differentiation, rather than proliferation. However, a combination of these two did not have a synergistic effect on differentiation. In other words, mechanical loading did not stimulate the differentiation of TMSCs with TGF-β3 supplementation. The effect of mechanical loading with TGF-β3 treatment on TMSC differentiation can be manipulated according to the differentiation stage of TMSCs. Moreover, TMSCs have the potential to be used for cell banking, and compared to other mesenchymal stem cells, they can be procured from patients via less invasive procedures. [ABSTRACT FROM AUTHOR]

Background: The multifunctional transforming growth factor beta (TGF-β) is a glycoprotein that exists in three isoforms. TGF-β3 expression increases in fetal wound healing and reduces fibronectin and collagen I and III deposition, and also improves the architecture of the neodermis which is a combination of blood vessels and connective tissue during wound healing. Fibroblasts are key cells in the wound healing process. TGF-β3 plays a critical role in scar-free wound healing and fibroblast actions in the wound healing process. The aim of this study was to express the TGF-β3 gene (tgf-b3) in human foreskin fibroblasts (HFF’s). Methods: We obtained HFF’s from a newborn and a primary fibroblast culture was prepared. The cells were transfected with TGF-β3-pCMV6-XL5 plasmid DNA by both lipofection and electroporation. Expression of TGF-β3 was measured by enzyme-linked immunosorbent assay (ELISA). Results: The highest TGF-β3 expression (8.3-fold greater than control) was obtained by lipofection after 72 hours using 3 μl of transfection reagent. Expression was 1.4-fold greater than control by electroporation. Conclusions: In this study, we successfully increased TGF-β3 expression in primary fibroblast cells. In the future, grafting these transfected fibroblasts onto wounds can help the healing process without scarring.

Background: The multifunctional transforming growth factor beta (TGF-β) is a glycoprotein that exists in three isoforms. TGF-β3 expression increases in fetal wound healing and reduces fibronectin and collagen I and III deposition, and also improves the architecture of the neodermis which is a combination of blood vessels and connective tissue during wound healing. Fibroblasts are key cells in the wound healing process. TGF-β3 plays a critical role in scar-free wound healing and fibroblast actions in the wound healing process. The aim of this study was to express the TGF-β3 gene (tgf-b3) in human foreskin fibroblasts (HFF's). Methods: We obtained HFF's from a newborn and a primary fibroblast culture was prepared. The cells were transfected with TGF-β3-pCMV6-XL5 plasmid DNA by both lipofection and electroporation. Expression of TGF-β3 was measured by enzyme-linked immunosorbent assay (ELISA). Results: The highest TGF-β3 expression (8.3-fold greater than control) was obtained by lipofection after 72 hours using 3 μl of transfection reagent. Expression was 1.4-fold greater than control by electroporation. Conclusions: In this study, we successfully increased TGF-β3 expression in primary fibroblast cells. In the future, grafting these transfected fibroblasts onto wounds can help the healing process without scarring. [ABSTRACT FROM AUTHOR]

The cleft palate presented by transforming growth factor-β3 (Tgf-β3) null mutant mice is caused by altered palatal shelf adhesion, cell proliferation, epithelial-to-mesenchymal transformation and cell death. The expression of epidermal growth factor (EGF), transforming growth factor-β1 (Tgf-β1) and muscle segment homeobox-1 (Msx-1) is modified in the palates of these knockout mice, and the cell proliferation defect is caused by the change in EGF expression. In this study, we aimed to determine whether this change in EGF expression has any effect on the other mechanisms altered in Tgf-β3 knockout mouse palates. We tested the effect of inhibiting EGF activity in vitro in the knockout palates via the addition of Tyrphostin AG 1478. We also investigated possible interactions between EGF, Tgf-β1 and Msx-1 in Tgf-β3 null mouse palate cultures. The results show that the inhibition of EGF activity in Tgf-β3 null mouse palate cultures improves palatal shelf adhesion and fusion, with a particular effect on cell death, and restores the normal distribution pattern of Msx-1 in the palatal mesenchyme. Inhibition of TGF-β1 does not affect either EGF or Msx-1 expression. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The blood–brain barrier (BBB) is a functional structure which regulates and restricts the transfer of circulating molecules and immune cells into the central nervous system. The barrier is formed by the presence of tight junctions (TJ) between the specialized brain endothelial cells. The volatile anesthetic isoflurane may affect the permeability of the BBB. Previous studies have proven that isoflurane alters hypoxia-inducible factor-1α (HIF-1α) expression, which may affect the TJ proteins; however, the mechanism of how TJ proteins are affected by isoflurane is still unclear. Primary human brain vascular endothelial cells (HBVEC) were exposed to isoflurane at various concentrations (0–2.5%) and different time periods (0–6h). The cell viability, occludin expression, paracellular permeability, VEGF expression, TGF-β3 expression and occludin protein endocytosis were quantified. Isoflurane treatment induced a time- and concentration-dependent decrease in occludin mRNA and protein levels in HBVEC. This effect was partially abrogated by silencing the HIF-1α expression. Isoflurane could activate HIF-1α, and the overexpression HIF-1α up-regulated the level of VEGF and TGF-β3, VEGF decreased the expression of occludin and TGF-β3 accelerated the endocytosis of occludin. RNA interference targeting HIF-1α reduced both VEGF and TGF-β3 expression after isoflurane treatment. Conclusion: This study provides direct evidence in vitro that exposing isoflurane to HBVECs can trigger HIF-1α activation, leading to lower protein levels of occludin, and increased permeability of the BBB. [Copyright &y& Elsevier]

Highlights: [•] EMP exposure with 400 pulses causes testicular tissue degeneration and exfoliation. [•] EMP exposure with 400 pulses increase apoptotic rate of testicular tissue. [•] EMP exposure with 400 pulses increases the TGF-β3 expression in testicular tissue. [•] TGF-β3 has regulatory functions in the increase in BTB permeability induced by EMP. [ABSTRACT FROM AUTHOR]

Introduction: Different approaches for disc regeneration are currently under investigation. Beside gene therapy and tissue engineering techniques, the application of growth and differentiation factors own promising potential. Studies using reduced intervertebral disc models, such as cell or tissue fragment cultures, have limited validity and show controversial results depending on the employed experimental model. Therefore, the goal of the current study was to investigate the effect of BMP-2 and TGF-β3 on intervertebral disc degeneration using an in vitro full-organ disc/endplate culture system. Materials and methods: Intervertebral rabbit disc explants were cultured in the presence of 1 μg/ml BMP-2 or TGF-β3 for 21 days in DMEM/F12 media. Nucleus and annulus were analyzed for gene expression of collagen type I and II (Col I/II), aggrecan, collagenases (MMP-1/MMP-13) with RT-qPCR, histological changes with bone and proteoglycan-specific staining (von Kossa, toluidine blue) and differences in cellularity (DNA) and proteoglycan content (alcian blue binding assay). Results: The results demonstrate that disc proteoglycan concentration decreased with time in the TGF-β3 and BMP-2 groups. In the annulus fibrosus (AF), TGF-β3 and BMP-2 resulted in an up-regulation of Col I and type II, and of aggrecan gene expression. In contrast, MMP genes were inhibited. In the nucleus, the growth factors decreased gene expression of aggrecan and spontaneous Col I up-regulation was inhibited by TGF-β3, whereas expression of Col II was decreased with BMP-2. There was no effect on expression of MMP-1 and MMP-13 for most sampling points. However, TGF-β3 and BMP-2 induced ossification of the AF was demonstrated by histology. Conclusion: It can be concluded that both growth factors, at the tested concentrations, may not be suitable to regenerate the whole intervertebral disc organ but they are interesting candidates for being injected alone or in combination into a painful intervertebral disc to induce osseous fusion (spondylodesis). [ABSTRACT FROM AUTHOR]

Abstract: Transforming growth factor-β (TGF-β) is the prototype of a family of secreted polypeptide growth factors. These cytokines play very important roles during development, as well as in normal physiological and disease processes, by regulating a wide array of cellular processes, such as cell growth, differentiation, migration, apoptosis, and extracellular matrix production. TGF-β utilizes a multitude of intracellular signalling pathways in addition to Smads with actions that are dependent on circumstances, including dose, target cell type, and context. The aims of this research were (i) to verify the effects of dose-dependent TGF-β3 treatment on YY1 and p53 expression, in BPH-1 cell line, human benign prostate hyperplasia, and two prostate cancer cell lines, LNCaP, which is androgen-sensitive, and DU-145, which is androgen-non responsive, (ii) establish a correlation between p53 and YY1 and (iii) determine the expression of a number of important intracellular signalling pathways in TGF-β3-treated prostate cell lines. The expression of YY1, p53, PI3K, AKT, pAKT, PTEN, Bcl-2, Bax, and iNOS was evaluated through Western blot analysis on BPH-1, LNCaP, and DU-145 cultures treated with 10 and 50ng/ml of TGF-β3 for 24h. The production of nitric oxide (NO) was determined by Griess reagent and cell viability through MTT assay. The results of this research demonstrated profound differences in the responses of the BPH-1, LNCaP, and DU-145 cell lines to TGF-β3 stimulation. We believe that the findings could be important because of the clinical relevance that they may assume and the therapeutic implications for TGF-β treatment of prostate cancer. [Copyright &y& Elsevier]

Objective: To investigate the regulation of early growth response-2 (Egr-2) by transforming growth factor β3 (TGF-β3) and its functions in cultured human uterine leiomyoma smooth muscle cells.Design: Laboratory research.Setting: Academic medical center.Patient(s): Primary leiomyoma cells from patients with symptomatic leiomyomata.Intervention(s): Tissue culture followed by RNA and protein analysis.Main Outcome Measure(s): Cell proliferation, alteration in extracellular matrix component expression.Result(s): In vivo mRNA levels of Egr-2 were statistically significantly higher in leiomyoma tissues compared with matched myometrial tissues, and showed a statistically significant correlation with TGF-β3 messenger RNA (mRNA) levels in leiomyoma tissues. In primary leiomyoma smooth muscle cells, TGF-β3 statistically significantly induced Egr-2 gene expression in a dose-dependent and time-dependent manner. Small interfering RNA (siRNA) knockdown of Egr-2 markedly increased the level of the proliferation marker proliferating cell nuclear antigen and the expression of proto-oncogene c-myc. On the other hand, ablation of Egr-2 stimulated collagen-1A1 and collagen-3A1 transcription and inhibited dermatopontin gene expression. However, the mRNA levels of α-smooth muscle actin and fibronectin were not affected by Egr-2 knockdown.Conclusion(s): We demonstrated that TGF-β3 regulated Egr-2 gene expression and presented evidence that Egr-2 decreases collagen production and stimulates dermatopontin gene expression. [ABSTRACT FROM AUTHOR]

Abstract: The canonical Wnt/β-catenin signaling plays essential role in development and diseases. Previous studies have implicated the canonical Wnt/β-catenin signaling in the regulation of normal palate development, but functional Wnt/β-catenin signaling and its tissue-specific activities remain to be accurately elucidated. In this study, we show that functional Wnt/β-catenin signaling operates primarily in the palate epithelium, particularly in the medial edge epithelium (MEE) of the developing mouse palatal shelves, consistent with the expression patterns of β-catenin and several Wnt ligands and receptors. Epithelial specific inactivation of β-catenin by the K14-Cre transgenic allele abolishes the canonical Wnt signaling activity in the palatal epithelium and leads to an abnormal persistence of the medial edge seam (MES), ultimately causing a cleft palate formation, a phenotype resembling that in Tgfβ3 mutant mice. Consistent with this phenotype is the down-regulation of Tgfβ3 and suppression of apoptosis in the MEE of the β-catenin mutant palatal shelves. Application of exogenous Tgfβ3 to the mutant palatal shelves in organ culture rescues the midline seam phenotype. On the other hand, expression of stabilized β-catenin in the palatal epithelium also disrupts normal palatogenesis by activating ectopic Tgfβ3 expression in the palatal epithelium and causing an aberrant fusion between the palate shelf and mandible in addition to severely deformed palatal shelves. Collectively, our results demonstrate an essential role for Wnt/β-catenin signaling in the epithelial component at the step of palate fusion during palate development by controlling the expression of Tgfβ3 in the MEE. [Copyright &y& Elsevier]

Abstract: The blood–testis barrier (BTB) plays an important role in male reproductive system. Lots of environmental stimulations can increase the permeability of BTB and then result in antisperm antibody (AsAb) generation, which is a key step in male immune infertility. Here we reported the results of male mice exposed to electromagnetic pulse (EMP) by measuring the expression of tight-junction-associated proteins (ZO-1 and Occludin), vimentin microfilaments, and transforming growth factor-beta (TGF-β3) as well as AsAb level in serum. Male BALB/c mice were sham exposed or exposed to EMP at two different intensities (200kV/m and 400kV/m) for 200 pulses. The testes were collected at different time points after EMP exposure. Immunofluorescence histocytochemistry, western blotting, laser confocal microscopy and RT-PCR were used in this study. Compared with sham group, the expression of ZO-1 and TGF-β3 significantly decreased accompanied with unevenly stained vimentin microfilaments and increased serum AsAb levels in EMP-exposed mice. These results suggest a potential BTB injury and immune infertility in male mice exposed to a certain intensity of EMP. [ABSTRACT FROM AUTHOR]

Abstract: Prenatal exposure to diazepam, a prototype sedative drug that belongs to Benzodiazepines, can lead to orofacial clefting in human newborns. By using real-time PCR, in the present study we investigated whether diazepam elicits gene expression alterations in extracellular matrix (ECM) components, growth factors and gamma-aminobutyric acid receptor (GABRB3), implicated in the coordinate regulation of palate development. Palate fibroblasts were treated with diazepam (Dz-N fibroblasts) and compared to cleft lip-palate (CLP) fibroblasts obtained from patients with no known exposure to diazepam or other teratogens. Untreated fibroblasts from non-CLP patients were used as control. The results showed significant convergences in gene expression pattern of collagens, fibromodulin, vitronectin, tenascin C, integrins and metalloprotease MMP13 between Dz-N and CLP fibroblasts. Among the growth factors, constitutive Fibroblast Growth Factor 2 (FGF2) was greatly enhanced in Dz-N and CLP fibroblasts and associated with a higher reduction of FGF receptor. Transforming Growth Factor beta 3 (TGFβ3) resulted up-regulated in CLP fibroblasts and decreased in Dz-N fibroblasts. We found phenotypic differences exhibited by Dz-N and CLP fibroblasts in GABRB3 gene regulation, so further studies are necessary to determine whether GABAergic system could be involved in the development of diazepam mediated CLP phenotype. Taken together the results elucidate the molecular mechanisms underlying possible toxicology effects induced by diazepam. Counselling of women on the safety of diazepam exposure is clinically important, also for the forensic consequences. [Copyright &y& Elsevier]

Abstract: We previously reported evidence that patients with periodontitis have serum antibodies to oral Gram positive bacteria that are cross-reactive with epithelial antigens, including CD24. High level expression of CD24 was confined to the reactive periodontal epithelium and inflamed gingival attachment. As a model for the reactive epithelium of chronic periodontitis, H413 epithelial cells derived from a human oral squamous cell carcinoma were cloned and lines expressing high levels of CD24 were selected. RNA interference protocols were designed to determine if CD24 could modulate intercellular interactions and regulate the biology of these epithelial cells. Knock-down of CD24 protein was demonstrated by Western blot and flow cytometry. The level of mRNA for CD24 was reduced 90% by RNAi treatment as assayed by real-time, reverse transcriptase (RT)-PCR. Gene products known to be important in epithelial biology, including E-cadherin and TGF-β3 that were demonstrated to undergo altered expression patterns in the periodontal lesion, were investigated. Down-regulation of CD24 mRNA was associated with reduced e-cadherin expression and up-regulated expression of snail, twist, and tgf-β3. The cells were treated with monoclonal antibodies to CD24 to mimic the action of auto-reactive antibodies to CD24 detected in affected patients. Relative to isotype control antibody, stimulation by anti-CD24 antibodies induced up-regulated expression of e-cadherin and down-regulation of tgf-β3 as assessed by real-time RT-PCR. No consistent changes for expression of β-catenin, connexins, integrins, icam-1, tgf-β1 or tgf-β2 were observed. CD24 could play an important role in modulating expression of genes that regulate epithelial differentiation in periodontal disease. [Copyright &y& Elsevier]

Objective To compare the mRNA levels of transforming growth factor beta (TGF-β) isoforms 1, 2, and 3 among surgically injured peritoneum that healed with adhesions, surgically injured peritoneum that healed without adhesions, and uninjured peritoneum. Design Prospective experimental study. Setting University vivarium. Animal(s) Fourteen sexually mature female Sprague-Dawley rats, 226–250 grams. Interventions(s) Standardized cecal abrasion was performed on 120 Sprague-Dawley rats. The areas of abrasion and any resultant adhesions were harvested at necropsy 7 days later. Total RNA was then extracted from the serosal adhesions of four rats, from the serosa of five rats that healed without adhesion formation, and from analogous areas of cecum from five rats that did not undergo abrasion and served as controls. Main outcome measure(s) Quantification of the expression of the TGF-β1, TGF-β2, and TGF-β3 mRNA transcripts in peritoneal adhesions, normally healed peritoneum, and fresh, uninjured peritoneal tissue through the use of multiplex reverse transcriptase–polymerase chain reaction analysis. Results(s) Peritoneal adhesion TGF-β1 and TGF-β3 mRNA expression was 3.7-fold and 8.6-fold higher, respectively, than in abraded tissues that healed normally; and 5.6-fold and 4.6-fold higher, respectively, than in nonabraded tissues. While TGF-β2 mRNA levels were also higher in serosal adhesions compared with normally healed and uninjured peritoneum, this rise was not statically significant. Conclusion(s) Peritoneal adhesions resulting from surgical abrasion of a serosal surface have statistically significant increased levels of TGF-β1 and -β3 mRNA transcripts compared with both uninjured and normally healed peritoneum. [ABSTRACT FROM AUTHOR]