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TGF-β1-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis
- Source :
- American journal of physiology. Renal physiology. 314(2)
- Publication Year :
- 2017
-
Abstract
- The characteristic features of chronic peritoneal injury with peritoneal dialysis (PD) are submesothelial fibrosis and neoangiogenesis. Transforming growth factor (TGF)β and vascular endothelial growth factor (VEGF)-A are the main mediators of fibrosis and neoangiogenesis, respectively; however, the effect of the interaction between them on the peritoneum is not well known. In this study, we investigated the relationship between TGF-β1 and VEGF-A in inducing peritoneal fibrosis by use of human tissues and dialysate, cultured cells, and animal models. The VEGF-A concentration correlated with the dialysate-to-plasma ratio of creatinine (D/P Cr) ( P < 0.001) and TGF-β1 ( P < 0.001) in human PD effluent. VEGF-A mRNA levels increased significantly in the peritoneal tissues of human ultrafiltration failure (UFF) patients and correlated with number of vessels ( P < 0.01) and peritoneal thickness ( P < 0.001). TGF-β1 increased VEGF-A production in human mesothelial cell lines and fibroblast cell lines, and TGF-β1-induced VEGF-A was suppressed by TGF-β receptor I (TGFβR-I) inhibitor. Incremental peak values of VEGF-A mRNA stimulated by TGF-β1 in human cultured mesothelial cells derived from PD patients with a range of peritoneal membrane functions correlated with D/P Cr ( P < 0.05). To evaluate the regulatory mechanisms of VEGF-A and neoangiogenesis in vivo, we administered TGFβR-I inhibitor intraperitoneally in a rat chlorhexidine-induced peritoneal injury (CG) model. TGFβR-I inhibitor administration in the CG model decreased peritoneal thickness ( P < 0.001), the number of vessels ( P < 0.001), and VEGF-A levels ( P < 0.05). These results suggest that neoangiogenesis is associated with fibrosis through the TGF-β1-VEGF-A pathway in mesothelial cells and fibroblasts. These findings are important when considering the strategy for management of UFF in PD patients.
- Subjects :
- 0301 basic medicine
Male
Vascular Endothelial Growth Factor A
Pathology
medicine.medical_specialty
Physiology
medicine.medical_treatment
VEGF receptors
030232 urology & nephrology
Receptor, Transforming Growth Factor-beta Type I
Angiogenesis Inhibitors
Ultrafiltration failure
Peritoneal dialysis
Cell Line
Rats, Sprague-Dawley
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Fibrosis
medicine
Animals
Humans
In patient
Amino Acids
Peritoneal Fibrosis
Aged
Aged, 80 and over
biology
Neovascularization, Pathologic
business.industry
Fibroblasts
Middle Aged
medicine.disease
Disease Models, Animal
030104 developmental biology
Xanthenes
biology.protein
Female
Peritoneum
business
Peritoneal Dialysis
Transforming growth factor
Signal Transduction
Subjects
Details
- ISSN :
- 15221466
- Volume :
- 314
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Renal physiology
- Accession number :
- edsair.doi.dedup.....77323e44ad3a49239857d4a10a6e4db3