Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Semaporin3A inhibitor ameliorates renal fibrosis through the regulation of JNK signaling

Semaporin3A inhibitor ameliorates renal fibrosis through the regulation of JNK signaling Renal fibrosis is the common pathological pathway in progressive renal diseases. In the study, we analyzed the roles of Semaphorin 3A (SEMA3A) on renal fibrosis and the effect of SEMA3A-inhibitor (SEMA3A-I) using unilateral ureteral obstruction (UUO) mouse model. The expression of SEMA3A in the proximal tubulus and neuropilin-1 (NRP1), a recepor of SEMA3A, in fibloblast and tubular cells were increased in the UUO kidneys. The increased expression of myofibroblast marker tenascin-C and fibronection as well as renal fibrosis were increased in UUO kidneys, all of which were ameliorated by SEMA3A-I. In addition, c-Jun N-terminal kinase (JNK) signaling pathway known as the target of SEMA3A signaling, was activated in proximal tubular cells and fibroblast cells after UUO surgery while SEMA3A-I significantly attenuated the activation. In vitro, treatments with SEMA3A as well as transforming growth factor-β1 (TGF-β1) in human proximal tubular cells lost epithelial cell characters while SEMA3A-I significantly ameliorated this transformation. JNK inhibitor, SP600125, partially reversed SEMA3A and TGF-β1-induced cell transformation, indicating that JNK signaling is involved in SEMA3A-induced renal fibrosis. In addition, the treatment with SEMA3A in fibroblast cells activated the expression of tenascin-C, collagen type I and fibronection, indicating that SEMA3A may accelerate renal fibrosis through the activation of fibroblast cells. The analysis of human data revealed the positive correlation between urinary SEMA3A and urinary N-acetyl-β-D-glucosaminidase, indicating the association between SEMA3A and tubular injury. In conclusion, SEMA3A signaling is involved in renal fibrosis through JNK signaling pathway and SEMA3A-I might be the therapeutic option for protecting from renal fibrosis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Physiology-Renal Physiology The American Physiological Society

Semaporin3A inhibitor ameliorates renal fibrosis through the regulation of JNK signaling

Loading next page...
 
/lp/the-american-physiological-society/semaporin3a-inhibitor-ameliorates-renal-fibrosis-through-the-nM3MJl660y

References (66)

ISSN
1931-857x
eISSN
1522-1466
DOI
10.1152/ajprenal.00234.2021
Publisher site
See Article on Publisher Site

Abstract

Renal fibrosis is the common pathological pathway in progressive renal diseases. In the study, we analyzed the roles of Semaphorin 3A (SEMA3A) on renal fibrosis and the effect of SEMA3A-inhibitor (SEMA3A-I) using unilateral ureteral obstruction (UUO) mouse model. The expression of SEMA3A in the proximal tubulus and neuropilin-1 (NRP1), a recepor of SEMA3A, in fibloblast and tubular cells were increased in the UUO kidneys. The increased expression of myofibroblast marker tenascin-C and fibronection as well as renal fibrosis were increased in UUO kidneys, all of which were ameliorated by SEMA3A-I. In addition, c-Jun N-terminal kinase (JNK) signaling pathway known as the target of SEMA3A signaling, was activated in proximal tubular cells and fibroblast cells after UUO surgery while SEMA3A-I significantly attenuated the activation. In vitro, treatments with SEMA3A as well as transforming growth factor-β1 (TGF-β1) in human proximal tubular cells lost epithelial cell characters while SEMA3A-I significantly ameliorated this transformation. JNK inhibitor, SP600125, partially reversed SEMA3A and TGF-β1-induced cell transformation, indicating that JNK signaling is involved in SEMA3A-induced renal fibrosis. In addition, the treatment with SEMA3A in fibroblast cells activated the expression of tenascin-C, collagen type I and fibronection, indicating that SEMA3A may accelerate renal fibrosis through the activation of fibroblast cells. The analysis of human data revealed the positive correlation between urinary SEMA3A and urinary N-acetyl-β-D-glucosaminidase, indicating the association between SEMA3A and tubular injury. In conclusion, SEMA3A signaling is involved in renal fibrosis through JNK signaling pathway and SEMA3A-I might be the therapeutic option for protecting from renal fibrosis.

Journal

American Journal of Physiology-Renal PhysiologyThe American Physiological Society

Published: Dec 1, 2021

There are no references for this article.