Up-regulation of the human-specific CHRFAM7A gene protects against renal fibrosis in mice with obstructive nephropathy.
Up-regulation of the human-specific CHRFAM7A gene protects against renal fibrosis in mice with obstructive nephropathy.
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上调人类特异性 CHRFAM7A 基因可预防梗阻性肾病小鼠的肾纤维化
DOI：
10.1111/jcmm.17630
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发表时间：
2023-01
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
肾纤维化是慢性肾脏疾病进展的主要因素。梗阻性肾病是肾纤维化的常见原因，也伴有炎症。为了探索人类特异性CHRFAM 7A表达（一种炎症相关基因）对梗阻性肾病期间肾纤维化的影响，我们研究了CHRFAM 7A转基因小鼠和经历单侧输尿管梗阻（UUO）损伤的野生型小鼠。CHRFAM 7A基因的转基因过表达抑制UUO诱导的肾纤维化，这通过减少纤维化基因表达和胶原沉积来证明。此外，与患有UUO的野生型小鼠相比，来自转基因小鼠的肾脏在UUO后具有降低的TGF-β1和Smad 2/3表达。此外，CHRFAM 7A的过表达减少了UUO损伤小鼠肾脏中炎性细胞因子的释放。在体外，CHRFAM 7A的过表达抑制TGF-β1诱导的人肾小管上皮细胞（HK-2细胞）中纤维化相关基因表达的增加。此外，HK-2细胞中CHRFAM 7A的上调表达减少了TGF-β1诱导的上皮间质转化（EMT），并抑制了TGF-β1/Smad 2/3信号通路的激活。总之，我们的研究结果表明，人类特异性CHRFAM 7A基因的过表达可以通过抑制TGF-β1/Smad 2/3信号通路减少肾小管上皮细胞的炎症反应和EMT来减少UUO诱导的肾纤维化。
Renal fibrosis is a major factor in the progression of chronic kidney diseases. Obstructive nephropathy is a common cause of renal fibrosis, which is also accompanied by inflammation. To explore the effect of human‐specific CHRFAM7A expression, an inflammation‐related gene, on renal fibrosis during obstructive nephropathy, we studied CHRFAM7A transgenic mice and wild type mice that underwent unilateral ureteral obstruction (UUO) injury. Transgenic overexpression of CHRFAM7A gene inhibited UUO‐induced renal fibrosis, which was demonstrated by decreased fibrotic gene expression and collagen deposition. Furthermore, kidneys from transgenic mice had reduced TGF‐β1 and Smad2/3 expression following UUO compared with those from wild type mice with UUO. In addition, the overexpression of CHRFAM7A decreased release of inflammatory cytokines in the kidneys of UUO‐injured mice. In vitro, the overexpression of CHRFAM7A inhibited TGF‐β1‐induced increase in expression of fibrosis‐related genes in human renal tubular epithelial cells (HK‐2 cells). Additionally, up‐regulated expression of CHRFAM7A in HK‐2 cells decreased TGF‐β1‐induced epithelial‐mesenchymal transition (EMT) and inhibited activation f TGF‐β1/Smad2/3 signalling pathways. Collectively, our findings demonstrate that overexpression of the human‐specific CHRFAM7A gene can reduce UUO‐induced renal fibrosis by inhibiting TGF‐β1/Smad2/3 signalling pathway to reduce inflammatory reactions and EMT of renal tubular epithelial cells.
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影响因子：
5.5
作者：
Cheng, JF;Encarnacion, MMD;Grande, JP
通讯作者：
Grande, JP
影响因子：
8.8
作者：
Ding, Hong;Xu, Yanyan;Jiang, Nan
通讯作者：
Jiang, Nan
影响因子：
4.8
作者：
de Lucas-Cerrillo, Ana M.;Constanza Maldifassi, M.;Montiel, Carmen
通讯作者：
Montiel, Carmen
影响因子：
6.1
作者：
Idasiak-Piechocka, Ilona;Oko, Andrzej;Czekalski, Stanislaw
通讯作者：
Czekalski, Stanislaw
影响因子：
168.9
作者：
Jha, Vivekanand;Garcia-Garcia, Guillermo;Yang, Chih-Wei
通讯作者：
Yang, Chih-Wei