Poricoic acid A as a modulator of TPH-1 expression inhibits renal fibrosis via modulating protein stability of β-catenin and β-catenin-mediated transcription.
Poricoic acid A as a modulator of TPH-1 expression inhibits renal fibrosis via modulating protein stability of β-catenin and β-catenin-mediated transcription.
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Poricoic Acid A 作为 TPH-1 表达的调节剂通过调节 β-catenin 和 β-catenin 介导的转录的蛋白质稳定性来抑制肾纤维化
DOI：
10.1177/2040622320962648
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发表时间：
2020
影响因子：
3.5
通讯作者：
Zhao YY
中科院分区：
文献类型：
--
作者：
Chen DQ;Wu XQ;Chen L;Hu HH;Wang YN;Zhao YY
Background: Renal fibrosis is the common feature of chronic kidney disease (CKD). However, few drugs specifically target fibrogenesis due to the lack of an effective therapeutic target. Hence, it is urgent to find a therapeutic strategy that inhibits renal fibrosis. Here, we identified that poricoic acid A (PAA) as the modulator of tryptophan hydroxylase-1 (TPH-1), the key enzyme in tryptophan metabolism, exerted potent anti-fibrotic effects in the kidney. Methods: Lentiviral vector, luciferase reporter activity assay and co-immunoprecipitation were used. The animal model of unilateral ureteral obstruction and adenine-induced chronic renal failure as well as transforming growth factor (TGF)-β1-treated epithelial cells NRK-52E and fibroblasts NRK-49F were used. Results: TPH-1 was gradually decreased during CKD progression, while PAA treatment significantly increased TPH-1 expression to suppress renal fibrosis. Pharmacological overexpression of TPH-1 by PAA treatment exhibited anti-fibrosis and was linked to Wnt/β-catenin signaling activity. TPH-1 exhibited anti-fibrotic effects by suppressing epithelial cell injury and fibroblast activation, and PAA promoted TPH-1 expression and then suppressed the Wnt/β-catenin signaling pathway via regulating the protein stability of β-catenin and β-catenin-mediated transcription. TPH-1 overexpression enhanced the anti-fibrotic effects of PAA, while TPH-1 deficiency weakened the anti-fibrotic effects of PAA, indicating that TPH-1 was required for the anti-fibrotic effects of PAA. Conclusion: PAA as a modulator of TPH-1 expression attenuated renal fibrosis through regulating the Wnt/β-catenin signaling pathway by acting on the protein stability of β-catenin and β-catenin-mediated transcription. TPH-1 was required for PAA to exert anti-fibrosis.
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影响因子：
3.7
作者：
Chu LY;Wang YF;Cheng HH;Kuo CC;Wu KK
通讯作者：
Wu KK
DOI：
10.1038/nrneph.2016.54
发表时间：
2016-07
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Edeling M;Ragi G;Huang S;Pavenstädt H;Susztak K
通讯作者：
Susztak K
影响因子：
--
作者：
Cheng HH;Chu LY;Chiang LY;Chen HL;Kuo CC;Wu KK
通讯作者：
Wu KK
茯苓酸 A 激活 AMPK 减弱肾纤维化过程中成纤维细胞的活化和异常细胞外基质重塑
影响因子：
7.9
作者：
Chen, Dan-Qian;Wang, Yan-Ni;Zhao, Ying-Yong
通讯作者：
Zhao, Ying-Yong
影响因子：
168.9
作者：
Jha, Vivekanand;Garcia-Garcia, Guillermo;Yang, Chih-Wei
通讯作者：
Yang, Chih-Wei