足细胞
肾小球基底膜
细胞生物学
转化生长因子
基底膜
MAPK/ERK通路
p38丝裂原活化蛋白激酶
化学
生物
肾
内科学
信号转导
肾小球肾炎
内分泌学
医学
蛋白尿
作者
Takahiro Ishikawa,Minoru Takemoto,Yoshihiro Akimoto,Aki Takada‐Watanabe,Kunimasa Yan,Kenichi Sakamoto,Yoshiro Maezawa,Miyuki Suguro,Liqun He,Karl Tryggvason,Christer Betsholtz,Koutaro Yokote
标识
DOI:10.1007/s00109-021-02050-w
摘要
Not 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.
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