title: Telmisartan attenuates peritoneal fibrosis via peroxisome proliferator-activated receptor-γ activation in rats.
abstract: Peritoneal dialysis (PD) is an effective treatment for patients with end-stage renal diseases, but long-term continuous PD causes peritoneal fibrosis (PF). This study aims to evaluate the anti-fibrotic effect of telmisartan on a rat model of PF and to investigate the underlying mechanisms. Five-sixths kidney nephrectomy and PD were used to establish the PF rat model. Glucose (2.5%) was used to establish an in vitro model in rat peritoneal mesothelial cells (PMC). Haematoxylin-eosin staining was used to examine the structural alterations. Masson's trichrome staining was used to observe the tissue fibrosis in peritoneal membrane of rats. Real-time polymerase chain reaction was used to measure messenger RNA expressions of profibrotic factors. Western blotting was used to determine protein expressions of profibrotic factors, peroxisome proliferator-activated receptor-γ, and mitogen-activated protein kinases (MAPK). Results demonstrated that administration of telmisartan dose-dependently attenuated the thickening of the peritoneal membrane and the fibrosis induced by long-term PD fluid exposure in rats. In addition, telmisartan treatment inhibited the upregulation of profibrotic factors induced by PD in the peritoneum of rats and by high-concentration glucose in PMC. Telmisartan was also effective in inhibiting PD and high-concentration, glucose-induced phosphorylation of MAPK in the peritoneum and PMC. Furthermore, peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 blocked these protective effects of telmisartan in PMC. The results suggest that telmisartan is effective in attenuating PD-induced PF, and this effect may be associated with the inhibition of profibrotic factor expression and MAPK phosphorylation via PPARγ activation.
authors: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Xuesong
authors: X
authors: Su
authors: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Rui
authors: R
authors: Yu
authors: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Xu
authors: X
authors: Yang
authors: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Guangyu
authors: G
authors: Zhou
authors: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Yanqiu
authors: Y
authors: Wang
authors: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Li
authors: L
authors: Li
authors: Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Detian
authors: D
authors: Li
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008297:Male; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056627:Peritoneal Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D000077333:Telmisartan
keywords: mitogen-activated protein kinase; peritoneal fibrosis; peritoneal mesothelial cells; peroxisome proliferator-activated receptor-γ; telmisartan