A novel podocyte protein, R3h domain containing-like, inhibits TGF-β-induced p38 MAPK and regulates the structure of podocytes and glomerular basement membrane
A novel podocyte protein, R3h domain containing-like, inhibits TGF-β-induced p38 MAPK and regulates the structure of podocytes and glomerular basement membrane
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DOI：
10.1007/s00109-021-02050-w
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发表时间：
2021-02-23
影响因子：
4.7
通讯作者：
Yokote，Koutaro
中科院分区：
文献类型：
--
作者：
Ishikawa，Takahiro;Takemoto，Minoru;Yokote，Koutaro
摘要 肾小球足细胞不仅在肾小球生理功能中发挥着重要作用，而且在肾小球病理尤其是糖尿病状态下也发挥着关键作用。因此，增加我们对足细胞表达的基因和蛋白质的了解非常重要。最近，我们鉴定了一种新的足细胞表达基因，R3h 结构域样基因（R3hdml），并分析了其体内和体外功能。转化生长因子-β (TGF-β) 信号调节 R3hdml 的表达。 R3hdml 抑制 TGF-β 诱导的 p38 丝裂原激活蛋白激酶磷酸化，从而改善足细胞凋亡。此外，小鼠中 R3hdml 的缺乏会显着恶化链脲佐菌素 (STZ) 诱导的糖尿病中的肾小球功能，而 R3hdml 的过度表达可改善 STZ 诱导的糖尿病中的蛋白尿。我们的结果推测，R3hdml 的功能分析可能会导致未来糖尿病肾病新治疗策略的开发。关键信息• 鉴定出一种新的足细胞表达蛋白 R3h 结构域样。• R3HDML 通过抑制 TGF-β 介导的 p38 MAPK 信号传导来抑制足细胞凋亡。• R3HDML 的过度表达可改善 STZ 诱导的糖尿病小鼠中的蛋白尿。• R3HDML 可能被证明是一种新的治疗方法糖尿病肾病的策略。
AbstractNot only in kidney glomerular physiological function but also glomerular pathology especially in diabetic condition, glomerular podocytes play pivotal roles. Therefore, it is important to increase our knowledge about the genes and proteins expressed in podocytes. Recently, we have identified a novel podocyte-expressed gene, R3h domain containing-like (R3hdml) and analyzed its function in vivo as well as in vitro. Transforming growth factor-β (TGF-β) signaling regulated the expression of R3hdml. And R3hdml inhibited p38 mitogen-activated protein kinase phosphorylation, which was induced by TGF-β, leading to the amelioration of podocyte apoptosis. Furthermore, a lack of R3hdml in mice significantly worsened glomerular function in streptozotocin (STZ)-induced diabetes, while overexpression of R3hdml ameliorated albuminuria in STZ-induced diabetes. Our results surmise that the functional analyses of R3hdml may lead to the development of novel therapeutic strategies for diabetic nephropathy in the future.Key messages• A novel podocyte expressed protein R3h domain containing-like was identified.• R3HDML inhibits podocyte apoptosis by inhibiting TGF-β-mediated p38 MAPK signaling.• Overexpression of R3HDML ameliorates albuminuria in STZ-induced diabetes mice.• R3HDML may prove to be a novel therapeutic strategy for diabetic nephropathy.