scholarly journals Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via TGF-β1-Smad-ILK pathway in unilateral ureteral obstruction rats

2018 ◽  
Author(s):  
Fang-Hua Qi ◽  
Ping-Ping Cai ◽  
Xiang Liu ◽  
Guo-Min Si
Keyword(s):  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Unilateral Ureteral Obstruction ◽  
Mesenchymal Transition ◽  
Tgf Β1

Long noncoding RNA NEAT1 sponges miR-129 to modulate renal fibrosis by regulation of collagen type I

2020 ◽  
Vol 319 (1) ◽  
pp. F93-F105
Author(s):  
Chen Li ◽  
Yuan-Fei Liu ◽  
Chong Huang ◽  
Yan-Xia Chen ◽  
Cheng-Yun Xu ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Noncoding Rna ◽  
Collagen Type ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Collagen Type I ◽  
Unilateral Ureteral Obstruction ◽  
Type I ◽  
Mesenchymal Transition

The long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to promote liver fibrosis progression. However, its molecular mechanism in renal fibrosis was not elucidated. In the present study, an in vitro model of renal fibrosis was established with HK-2 and HKC-8 cells treated with transforming growth factor-β1. C57BL/6 mice were used for the in vivo model with unilateral ureteral obstruction. Our results indicated that NEAT1 and collagen type I levels were significantly upregulated, whereas miR-129 was obviously downregulated, in the progression of renal fibrosis. Meanwhile, NEAT1 knockdown or miR-129 overexpression inhibited collagen type I deposition, the epithelial-mesenchymal transition process, and the inflammation response to suppress renal fibrosis. NEAT1 directly targeted miR-129, and miR-129 directly bound to collagen type I. Downregulation of miR-129 reversed inhibition of renal fibrosis induced by NEAT1 silencing, and upregulation of collagen type I also reversed inhibition of renal fibrosis caused by miR-129 overexpression. NEAT1 knockdown alleviated renal fibrosis in mice subjected to unilateral ureteral obstruction. In conclusion, NEAT1 sponged miR-129 to modulate the epithelial-mesenchymal transition process and inflammation response of renal fibrosis by regulation of collagen type I. Our study indicates a novel role in the regulation of renal fibrosis and provides a new potential treatment target for renal fibrosis.

scholarly journals Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κB-TGF-β1/Smad Signaling Pathway

2020 ◽  
Vol 21 (2) ◽  
pp. 402 ◽  
Author(s):  
Yi Quan ◽  
Woong Park ◽  
Jixiu Jin ◽  
Won Kim ◽  
Sung Kwang Park ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Mitochondrial Dynamics ◽  
Unilateral Ureteral Obstruction ◽  
Sirtuin 3 ◽  
Smad Signaling ◽  
Renal Tubulointerstitial Fibrosis ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Renal fibrosis is a common feature of all progressive chronic kidney diseases. Sirtuin 3 (SIRT3) is one of the mitochondrial sirtuins, and plays a role in the regulation of mitochondrial biogenesis, oxidative stress, fatty acid metabolism, and aging. Recently, honokiol (HKL), as a pharmaceutical SIRT3 activator, has been observed to have a protective effect against pressure overload-induced cardiac hypertrophy by increasing SIRT3 activity. In this study, we investigated whether HKL, as a SIRT3 activator, also has protective effects against unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis through SIRT3-dependent regulation of mitochondrial dynamics and the nuclear factor-κB (NF-κB)/transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We found that HKL decreased the UUO-induced increase in tubular injury and extracellular matrix (ECM) deposition in mice. HKL also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells. Finally, we showed that HKL treatment decreased UUO-induced mitochondrial fission and promoted mitochondrial fusion through SIRT3-dependent effects. In conclusion, activation of SIRT3 via HKL treatment might have beneficial effects on UUO-induced renal fibrosis through SIRT3-dependent regulation of mitochondrial dynamics and the NF-κB/TGF-β1/Smad signaling pathway.

scholarly journals Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction

2017 ◽  
Vol 312 (1) ◽  
pp. F121-F133 ◽  
Author(s):  
Renfei Luo ◽  
Yutaka Kakizoe ◽  
Feifei Wang ◽  
Xiang Fan ◽  
Shan Hu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Collecting Duct ◽  
Unilateral Ureteral Obstruction ◽  
Prostaglandin E ◽  
Expression Levels ◽  
Collagen Iii ◽  
Tgf Β1

Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 to prostaglandin E2 (PGE2), plays an important role in a variety of inflammatory diseases. We investigated the contribution of mPGES-1 to renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) for 7 days using wild-type (WT) and mPGES-1 knockout (KO) mice. UUO induced increased mRNA and protein expression of mPGES-1 and cyclooxygenase-2 in WT mice. UUO was associated with increased renal PGE2 content and upregulated PGE2 receptor (EP) 4 expression in obstructed kidneys of both WT and mPGES-1 KO mice; EP4 expression levels were higher in KO mice with UUO than those in WT mice. Protein expression of NLRP3 inflammasome components ASC and interleukin-1β was significantly increased in obstructed kidneys of KO mice compared with that in WT mice. mRNA expression levels of fibronectin, collagen III, and transforming growth factor-β1 (TGF-β1) were significantly higher in obstructed kidneys of KO mice than that in WT mice. In KO mice, protein expression of fibronectin and collagen III was markedly increased in obstructed kidneys compared with WT mice, which was associated with increased phosphorylation of protein kinase B (AKT). EP4 agonist CAY10598 attenuated increased expression of collagen I and fibronectin induced by TGF-β1 in inner medullary collecting duct 3 cells. Moreover, CAY10598 prevented the activation of NLRP3 inflammasomes induced by angiotensin II in human proximal tubule cells (HK2). In conclusion, these findings suggested that mPGES-1 exerts a potentially protective effect against renal fibrosis and inflammation induced by UUO in mice.

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