4.5 Article

Semaporin3A inhibitor ameliorates renal fibrosis through the regulation of JNK signaling

期刊

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 321, 期 6, 页码 F740-F756

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00234.2021

关键词

c-Jun NH2-terminal kinase; myofibroblast; renal fibrosis; semaphorin3A

资金

  1. China Scholarship Council [201708210186]
  2. Japanese Society for the Promotion of Science (JSPS) [18K15978, 20K17283]
  3. Yukiko Ishibashi Foundation
  4. Sanyo Broadcasting Foundation
  5. Japanese Association of Dialysis Physicians [2019-9]
  6. grant for the patho-physiological research conference in chronic kidney disease [JKFB19-4]
  7. JSPS [18K08244]
  8. Grants-in-Aid for Scientific Research [18K15978, 20K17283, 18K08244] Funding Source: KAKEN

向作者/读者索取更多资源

Renal fibrosis, a common pathological process in renal diseases, was studied using a UUO mouse model, revealing increased SEMA3A signaling and its inhibition ameliorating fibrosis through JNK regulation. This study suggests SEMA3A inhibitor as a potential therapeutic option for renal fibrosis.
Renal fibrosis is the common pathological pathway in progressive renal diseases. In the present study, we analyzed the roles of semaphorin 3 A (SEMA3A) on renal fibrosis and the effect of SEMA3A inhibitor (SEMA3A-I) using a unilateral ureteral obstruction (UUO) mouse model. Expression of SEMA3A in the proximal tubulus and neuropilin-1, a recepor of SEMA3A, in fibloblast and tubular cells were increased in UUO kidneys. The 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, the JNK signaling pathway, known as the target of SEMA3A signaling, was activated in proximal tubular cells and fibroblast cells after UUO surgery, and SEMA3A-I significantly attenuated the activation. In vitro, treatments with SEMA3A as well as transforming growth factor-beta 1 (TGF-beta 1) in human proximal tubular cells lost epithelial cell characteristics, and SEMA3A-1 significantly ameliorated this transformation. The JNK inhibitor SP600125 partially reversed SEMA3A and TGF-beta 1-induced cell transformation, indicating that JNK signaling is involved in SEMA3A-induced renal fibrosis. In addition, treatment with SEMA3A in fibroblast cells activated expression of tenascin-C, collagen type I, and fibronection, indicating that SEMA3A may accelerate renal fibrosis through the activation of fibroblast cells. Analysis of human data revealed the positive correlation between urinary SEMA3A and urinary N-acetyl-beta-D-glucosaminidase, indicating the association between SEMA3A and tubular injury. In conclusion, SEMA3A signaling is involved in renal fibrosis through the JNK signaling pathway and SEMA3A-I might be a therapeutic option for protecting from renal fibrosis. NEW & NOTEWORTHY Renal fibrosis is the common pathological pathway in the progression of renal diseases. This study, using a unilateral ureteral obstruction (UUO) mouse model, indicated increased semaphorin3A (SEMA3A) signaling in renal tubular cells as well as fibroblast cells under UUO surgery, and SEMA3A inhibitor ameliorated UUO-induced renal fibrosis through the regulation of JNK signaling. The study proposes the potential therapeutic option of SEMA3A inhibitor to treat renal fibrosis.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据