Long non-coding RNA lnc-CHAF1B-3 promotes renal interstitial fibrosis by regulating EMT-related genes in renal proximal tubular cells.
Long non-coding RNA lnc-CHAF1B-3 promotes renal interstitial fibrosis by regulating EMT-related genes in renal proximal tubular cells.
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长链非编码RNA lnc-CHAF1B-3通过调控肾近端小管细胞emt相关基因促进肾间质纤维化。
DOI：
10.1016/j.omtn.2022.12.011
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发表时间：
2023-03-14
期刊：
影响因子：
--
通讯作者：
Maruyama, Shoichi
中科院分区：
文献类型：
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作者：
Imai, Kentaro;Ishimoto, Takuji;Doke, Tomohito;Tsuboi, Toshiki;Watanabe, Yu;Katsushima, Keisuke;Suzuki, Miho;Oishi, Hideto;Furuhashi, Kazuhiro;Ito, Yasuhiko;Kondo, Yutaka;Maruyama, Shoichi
肾间质纤维化（RIF）是慢性肾脏病常见的病理表现。肾小管上皮细胞的上皮间质转化（EMT）被认为是 RIF 的主要原因。尽管据报道长非编码RNA（lncRNA）参与各种病理生理过程，但lncRNA在RIF进展中的作用和潜在分子机制仍知之甚少。在这项研究中，我们研究了 RIF 中 lncRNA 的功能。微阵列检测显示，转化生长因子-β1 (TGF-β1) 和低氧刺激使人肾近端肾小管细胞中 lncRNA lnc-CHAF1B-3（也称为密蛋白 14 反义 RNA 1）的表达显着上调，同时 EMT 相关基因的表达增加。 lnc-CHAF1B-3的敲低显着抑制了TGF-β1诱导的I型胶原α1、钙粘蛋白-2、纤溶酶原激活剂抑制剂-1、蜗牛家族转录抑制子I (SNAI1)和SNAI2的上调表达。对 IgA 肾病患者石蜡包埋肾活检样本进行的定量逆转录酶 PCR 分析显示，lnc-CHAF1B-3 表达与尿蛋白水平呈正相关，与估计肾小球滤过率呈负相关。原位杂交表明lnc-CHAF1B-3仅在近端小管中表达。这些发现表明 lnc-CHAF1B-3 通过调节 EMT 相关信号传导影响 RIF 的进展。因此，lnc-CHAF1B-3是治疗RIF的潜在靶点。今井等人。发现 lncRNA lnc-CHAF1B-3 调节人肾近曲小管中 EMT 相关信号传导，并且肾脏 lnc-CHAF1B-3 表达与 IgA 肾病（包括间质纤维化）的疾病严重程度相关。因此，lnc-CHAF1B-3可能作为治疗肾纤维化的潜在靶点。
Renal interstitial fibrosis (RIF) is a common pathological manifestation of chronic kidney diseases. Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is considered a major cause of RIF. Although long non-coding RNAs (lncRNAs) are reportedly involved in various pathophysiological processes, the roles and underlying molecular mechanisms of lncRNAs in the progression of RIF are poorly understood. In this study, we investigated the function of lncRNAs in RIF. Microarray assays showed that expression of the lncRNA lnc-CHAF1B-3 (also called claudin 14 antisense RNA 1) was significantly upregulated in human renal proximal tubular cells by both transforming growth factor-β1 (TGF-β1) and hypoxic stimulation, accompanied with increased expression of EMT-related genes. Knockdown of lnc-CHAF1B-3 significantly suppressed TGF-β1-induced upregulated expression of collagen type I alpha 1, cadherin-2, plasminogen activator inhibitor-1, snail family transcriptional repressor I (SNAI1) and SNAI2. Quantitative reverse transcriptase PCR analyses of paraffin-embedded kidney biopsy samples from IgA nephropathy patients revealed lnc-CHAF1B-3 expression was correlated positively with urinary protein levels and correlated negatively with estimated glomerular filtration rate. In situ hybridization demonstrated that lnc-CHAF1B-3 is expressed only in proximal tubules. These findings suggest lnc-CHAF1B-3 affects the progression of RIF by regulating EMT-related signaling. Thus, lnc-CHAF1B-3 is a potential target in the treatment of RIF. Imai et al. found that a lncRNA, lnc-CHAF1B-3, regulates EMT-related signaling in human renal proximal tubules, and that renal lnc-CHAF1B-3 expression is associated with disease severity of IgA nephropathy, including interstitial fibrosis. Thus, lnc-CHAF1B-3 may serve as a potential target for the treatment of renal fibrosis.
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DOI：
10.1038/nrneph.2016.54
发表时间：
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期刊：
Nature reviews. Nephrology
影响因子：
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