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姜黄素介导的排斥性导向分子 B（RGMb）在单侧输尿管梗阻诱导的肾纤维化治疗机制中的作用。

Curcumin mediates repulsive guidance molecule B (RGMb) in the treatment mechanism of renal fibrosis induced by unilateral ureteral obstruction.

机构信息

Department of Nephrology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.

Nanchang University, Nanchang, China.

出版信息

Ren Fail. 2021 Dec;43(1):1496-1505. doi: 10.1080/0886022X.2021.1997764.

DOI:10.1080/0886022X.2021.1997764
PMID:34751624
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8583759/
Abstract

In this study, we explored the role and mechanism of repulsive guidance molecule B (RGMb, also known as Dragon) in the protective effects of curcumin against renal fibrosis and verified Dragon's effect on renal tubular epithelial cell apoptosis and cell programmability. Unilateral ureteral obstruction (UUO) was surgically induced in rats to establish a model of renal interstitial fibrosis (RIF). The rats were then treated with curcumin. Curcumin prominently decreased the serum creatinine (SCr) and blood urea nitrogen (BUN) levels, and also improved the tubular injury in the UUO-induced rats. Curcumin significantly downregulated the TGF-β1, P-Smad2/3, cleaved caspase-3, cleaved caspase-8 and Dragon levels. Dragon knockdown also markedly reduced the TGF-β1, P-Smad2/3, Smad2/3, cleaved caspase-3, cleaved caspase-8, fibronectin, collagen I, collagen IV, vimentin, and α-SMA expression levels. Conversely, Dragon overexpression caused higher expression levels of these proteins, and curcumin reversed this effect. Furthermore, Dragon knockdown increased the E-cadherin levels, whereas Dragon overexpression decreased these levels. Overexpressing Dragon significantly decreased the cell viability, and curcumin reversed this effect. In conclusion, curcumin acted on Dragon and attenuated RIF in UUO rat models. Curcumin downregulated the TGF-β1/Smad signaling pathway and inhibited Dragon and fibrogenic molecules in both rats and HK-2 cells.

摘要

在这项研究中，我们探讨了排斥性导向分子 B（也称为 Dragon）在姜黄素对肾纤维化保护作用中的作用和机制，并验证了 Dragon 对肾小管上皮细胞凋亡和细胞可编程性的影响。通过手术诱导单侧输尿管梗阻（UUO）建立肾间质纤维化（RIF）大鼠模型，然后用姜黄素进行治疗。姜黄素显著降低了血清肌酐（SCr）和血尿素氮（BUN）水平，改善了 UUO 诱导的大鼠肾小管损伤。姜黄素显著下调了 TGF-β1、P-Smad2/3、cleaved caspase-3、cleaved caspase-8 和 Dragon 水平。Dragon 敲低也显著降低了 TGF-β1、P-Smad2/3、Smad2/3、cleaved caspase-3、cleaved caspase-8、纤连蛋白、胶原 I、胶原 IV、波形蛋白和α-SMA 的表达水平。相反，Dragon 过表达导致这些蛋白的表达水平升高，而姜黄素则逆转了这种效应。此外，Dragon 敲低增加了 E-cadherin 水平，而 Dragon 过表达则降低了这些水平。过表达 Dragon 显著降低了细胞活力，而姜黄素则逆转了这种效应。总之，姜黄素作用于 Dragon，减轻 UUO 大鼠模型的 RIF。姜黄素下调 TGF-β1/Smad 信号通路，抑制 Dragon 和纤维化分子在大鼠和 HK-2 细胞中的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/63af2319ed58/IRNF_A_1997764_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/330fe66dd847/IRNF_A_1997764_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/c2c258d7752b/IRNF_A_1997764_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/d1f66193c9c4/IRNF_A_1997764_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/8dc5bac2b125/IRNF_A_1997764_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/63af2319ed58/IRNF_A_1997764_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/330fe66dd847/IRNF_A_1997764_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/c2c258d7752b/IRNF_A_1997764_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/d1f66193c9c4/IRNF_A_1997764_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/8dc5bac2b125/IRNF_A_1997764_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ae3/8583759/63af2319ed58/IRNF_A_1997764_F0005_C.jpg

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Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments.
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