| Autor: |
Jia-Yun, Ni, Xin, Wang, Hong-Yan, Xie, Ning-Hao, Yang, Jing-Yao, Li, Xi-Ang, Sun, Heng-Jiang, Guo, Li, Zhou, Wei, Zhang, Jun, Liu, Li-Min, Lu |
| Rok vydání: |
2022 |
| Zdroj: |
Acta pharmacologica Sinica. |
| ISSN: |
1745-7254 |
| Popis: |
Transforming growth factor-β1 (TGF-β1) is regarded as a key factor in promoting renal fibrosis during chronic kidney disease (CKD). Signaling transduction of TGF-β1 starts with binding to TGF-β type II receptor (Tgfbr2), a constitutively activated kinase that phosphorylates TGF-β type I receptor (Tgfbr1), and then activates downstream Smad2/3 or noncanonical pathways. Previous studies show that cellular senescence is associated with the progression of CKD, and accelerated tubular cell senescence is implicated in promoting renal fibrosis. In the present study we investigated the renal parenchymal cell senescence in fibrosis from the sight of posttranslational regulation and focused on Tgfbr2, the important gatekeeper for TGF-β1 downstream signaling. In mice with unilateral ureteral obstruction (UUO) and folic acid (FA)-induced fibrotic kidneys, we found that Tgfbr2 was markedly elevated without obvious change in its mRNA levels. As an important member of deubiquitinating enzymes, ubiquitin-specific protease 11 (Usp11) was also significantly increased in fibrotic kidneys, and co-distributed with Tgfbr2 in tubular epithelial cells. Pretreatment with Usp11 inhibitor mitoxantrone (MTX, 30 mg · kg |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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