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Cystic fibrosis is a disease caused by a mutation on the CFTR gene coding for a chloride channel. The dominant mutation F508del eliminates the CFTR protein at the surface of epithelial cells, causing an accumulation of viscous mucus in the airways. In advanced stages of the disease, respiratory failure is associated with cellular hypoxia. Our project aims not only to describe the impact of hypoxia on ion channels and to highlight the underlying signaling pathways involved, but also to test the effectiveness of current CF treatments under the above-mentioned conditions., (Copyright © 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Recent study established the role of integrins in keratinocyte growth factor (KGF)-induced oral epithelial adhesion and rete peg elongation. However, how extracellular matrix (ECM) remodeling cooperates with the increased epithelial adhesion during rete peg elongation has yet to be determined. Podosomes are cell-matrix contact structures that combine several abilities, including adhesion and matrix degradation. In the present study, we identified podosome formation at the ventral side of human immortalized oral epithelial cells (HIOECs) upon KGF treatment. Moreover, podosomal components including integrin α6，β4，α3，β1 and MMP14 colocalized with the F-actin-cortactin complex and matrix degradation assays demonstrated the ability of the F-actin-cortactin complex to degrade matrix. Inhibition both of integrin subunits β4 and β1 with specific blocking antibodies and inhibition of Erk1/2 abrogated the KGF-induced podosome formation. Notably, knockdown of integrin subunits β4 and β1 with specific small interfering RNA (siRNA) downregulated the phosphorylation levels of Erk1/2. In contrast, inhibition of both Erk1/2 could upregulate the expression of integrin subunits β4 and β1. These results demonstrate that KGF induces podosome formation via integrin-Erk1/2 signaling in HIOECs, suggesting a novel mechanism by which integrins enhance oral epithelial adhesion and rete peg elongation., (Copyright © 2019. Published by Elsevier Inc.)

The role of dendritic cells (DC) in the pathogenesis of allergic asthma and rhinitis has been highlighted for 15 years. In this review, we summarize key findings concerning DC function in airway allergy and focus on studies performed in human. DC coming from allergic patients have specific characteristics, including significant expression of high affinity receptor for IgE as well as a propensity for Th2 responses induction following priming with allergen and/or epithelial cytokines. Mechanistic data concerning this DC dysfunction in asthma also provide perspectives for innovating therapies., (© 2015 médecine/sciences – Inserm.)

Introduction: Epithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis., Background: The development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult., Conclusion: Identification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution., (Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Retinoic acid plays an essential role in lung development and is involved in all stages of embryogenesis and morphogenesis. We aimed to determine whether the human foetal lung is able to synthesize retinoic acid., Methods: ADH3, RALDH1 and CYP26B1 RNA were studied by qualitative and semi-quantitative RT-PCR in human lungs at different stages of development. In human alveolar epithelial cells (lines A549), RAR beta (induced by retinoic acid) was quantified, after treatment by retinol, by q-PCR at 24h and 48 h., Results: The expression of the RNA of ADH3, RALDH1 and CYP26B1 was detected for each of the four stages studied and in the A549 cell line. Only the level of RALDH1 RNA changed during the course of lung development. In the A549 cell line, treatment by retinol induced transcription of the RAR beta gene at 24 and 48 hours., Conclusion: The presence of ADH3, RALDH1 and CYP26B1 during the four stages of normal lung development and in the A549 cell line, as well as the capacity to convert retinol to retinoic acid in these cells, indicate that foetal human lung has the ability to regulate the supply of vitamin A from the pseudoglandular stage., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

In 1969, Brambell, while studying the long serum half-life of IgG and their ability to cross the materno-foetal barrier, attributed these two properties to the existence of a specific Fc receptor, which was later denominated FcRn for neonatal Fc receptor. The resolution of its structure revealed that it is a MHC class-I-like molecule. FcRn is able to load IgG and albumin in a pH-dependent manner. It acts as an intracellular transport protein and as such is controling the serum half-life of these proteins (apical recycling of IgG and albumin in endothelial cells), IgG biodistribution (apical to basolateral and basolateral to apical transport of IgG in epithelial and endothelial cells) and it may also contribute to phagocytosis. FcRn is thus a key partner in the pharmacokinetics of therapeutic antibodies, opening interesting prospects for optimisation of their use.

Considering that there is a shortage of organ donor, the aim of tissue engineering is to develop substitutes for the replacement of wounded or diseased tissues. Autologous tissue is evidently a preferable transplant material for long-term graft persistence because of the unavoidable rejection reaction occuring against allogeneic transplant. For the production of such substitutes, it is essential to control the culture conditions for post-natal human stem cells. Furthermore, histological organization and functionality of reconstructed tissues must approach those of native organs. For self-renewing tissues such as skin and cornea, tissue engineering strategies must include the preservation of stem cells during the in vitro process as well as after grafting to ensure the long-term regeneration of the transplants. We described a tissue engineering method named the self-assembly approach allowing the production of autologous living organs from human cells without any exogenous biomaterial. This approach is based on the capacity of mesenchymal cells to create in vitro their own extracellular matrix and then reform a tissue. Thereafter, various techniques allow the reorganization of such tissues in more complex organ such as valve leaflets, blood vessels, skin or cornea. These tissues offer the hope of new alternatives for organ transplantation in the future. In this review, the importance of preserving stem cells during in vitro expansion and controlling cell differentiation as well as tissue organization to ensure quality and functionality of tissue-engineered organs will be discussed, while focusing on skin and cornea.

Transcripts of more than 30 different K(+) channels have been detected in the respiratory epithelium lining airways and alveoli. These channels belong to the 3 main classes of K(+) channels, i.e. i) voltage-dependent or calcium-activated, 6 transmembrane segments (TM), ii) 2-pores 4-TM and iii) inward-rectified 2-TM channels. The physiological and functional significance of this high molecular diversity of lung epithelial K(+) channels is not well understood. Surprisingly, relatively few studies are focused on K(+) channel function in lung epithelial physiology. Nevertheless, several studies have shown that KvLQT1, KCa and K(ATP) K(+) channels play a crucial role in ion and fluid transport, contributing to the control of airway and alveolar surface liquid composition and volume. K(+) channels are involved in other key functions, such as O(2) sensing or the capacity of the respiratory epithelia to repair after injury. This mini-review aims to discuss potential functions of lung K(+) channels.

Despite the continuous and renewed interest in IPF, the precise biological mechanisms underlying the development of fibrosis and leading to the irreversible destruction of the lung are still unknown. Inflammation seems to play a minor role at the initiation of the disease. Identification of excessive apoptosis of alveolar epithelial cells led to the hypothesis that the disorder results from repeated alveolar epithelial cell injury and activation. In turn, alveolar epithelial cells induce the recruitment, proliferation, and activation of mesenchymal cells with the formation of fibroblastic foci and the abnormal accumulation of extracellular matrix. Fibroblastic foci are connected in a tridimensional reticulum. Circulating mesenchymal precursors called fibrocytes, and transdifferenciation of epithelial cells, endothelial cells and/or mesothelial cells, may all contribute to the accumulation of fibroblasts in the lung.

Introduction: The aim of this study was to evaluate and to compare the potential for wound healing of the buccal mucosa with the use of two mouth rinses; one containing 0.10% chlorhexidine with alcohol, the second containing 0.12% chlorhexidine without alcohol., Material and Method: Using a model of human buccal mucosa kept alive ex vivo, an immunohistochemical assessment of the mitotic potential of epithelial cells and a biochemical evaluation of the capacity of the fibroblasts of the gingival mucosa to synthesize collagen was performed., Results: A mouth rinse containing 0.10% chlorhexidine with alcohol (Eludril) did not alter the potential for epithelial proliferation and for collagen synthesis within the gingival chorion grown in survival conditions. The results revealed a significant difference between the two mouth rinses for each of the parameters studied. The most favourable results were obtained with the mouth rinse containing alcohol., Discussion: The presence of alcohol in a mouth rinse containing 0.10% chlorhexidine has no deleterious effects on healing capacity. On the contrary, it helps stimulate wound healing. The combination of chlorhexidine plus alcohol is superior for healing, chlorhexidine alone does not show any significant difference compared with the control.

Milk protein gene expression varies during the pregnancy/lactation cycle under the influence of lactogenic hormones which induce the activation of several transcription factors. Beyond this activation modifying the binding properties of these factors to their consensus sequences, their interactions with DNA is regulated by variations of the chromatin structure. In the nuclei of the mammary epithelial cell, the three dimensional organisation of the chromatin loops, located between matrix attachment regions, is now being studied. The main milk components are organised in supramolecular structures. Milk fat globules are made of a triglyceride core enwrapped by a tripartite membrane originating from various intracellular compartments. The caseins, the main milk proteins, form aggregates: the casein micelles. Their gradual aggregation in the secretory pathway is initiated as soon as from the endoplasmic reticulum. The mesostructures of the milk fat globule and of the casein micelle remain to be elucidated. Our goal is to make some progress into the understanding of the molecular and cellular mechanisms involved in the formation of these milk products.

The intestine is colonised by a vast population of resident bacteria which have established mutualistic relationships with their host throughout evolution, progressing from commensalism to symbiotic interactions. Intestinal bacteria benefit from resources available in their host, but reciprocally provide advantages to their host, by supplying enzymatic activities not encoded in the host genome, by promoting maturation of the intestine and of the gut associated immune system as well as by modifying the host metabolism. The commensal bacteria, although deprived of pathogenic attributes, might however become a danger for the host in case of translocation, acquisition of pathogenic features or via the inappropriate activation of intestinal inflammation. Remarkably, the commensal flora promotes the onset of innate and adaptive immune defences which, in turn, allow to set up a subtle balance between the host and the flora that promotes the symbiosis.

Mammary epithelium is organized as a bilayer with a layer of luminal secretory cells and a layer of basal myoepithelial cells. To dissect the specific functions of these two major compartments of the mammary epithelium in mammary morphogenesis we have used genetically modified mice carrying transgenes or conditional alleles whose expression or ablation were cell-type specific. Basal cells are located in close proximity to mammary stroma and directly interact with the extracellular matrix (basement membrane) during all their lifespan. On the contrary, luminal secretory cells during early stages of the postnatal mammary development have only limited contacts with basement membrane and become exposed to the extracellular matrix only during late developmental stages at the end of pregnancy and in lactation. Consistently perturbation of beta1-integrin function specifically in the luminal layer of the mammary epithelium, did not interfere with mammary morphogenesis until the second part of pregnancy but led to impaired secretory differentiation and lactation. On the contrary, ablation of beta1-integrin gene in the basal mammary epithelial cells resulted in a more precocious phenotype: disorganized branching in young virgin animals and a complete arrest of lobuloalveolar development. Further, a constitutive activation of beta-catenin signaling due to expression of N-terminally truncated (stabilized) beta-catenin specifically in basal myoepithelial cells resulted in accelerated differentiation of luminal secretory cells in pregnancy, precocious postlactational involution, increased angiogenesis and development of mammary tumors. Altogether these data suggest that basal mammary epithelial cells can affect growth and differentiation of luminal secretory cells, have an impact on the epithelium-stroma relationships and, thereby, play an important role in the process of mammary morphogenesis and differentiation.

Polarity is a fundamental characteristic of most eukaryotic cells. The plasma membrane of such cells consists in two structurally and functionally different domains, i.e., the basolateral and the apical membrane, separated by tight junctions. The generation of the distinct molecular identity of both domains and its maintenance in spite of the dynamics of lipids and proteins at either surface requires sophisticated sorting and trafficking mechanisms. Recent progress in the field of polarized trafficking reveals that, for a detailed understanding of its mechanism and regulation, an integrated approach that includes the flow of both lipids and proteins is imperative. In this review, some recent progress in understanding mechanisms involved in protein sorting and trafficking is discussed. We focus on the role of lipid microdomains (Rafts) in trafficking of proteins to the apical surface of polarized cells.