GADD45B Promotes Glucose-Induced Renal Tubular Epithelial-Mesenchymal Transition and Apoptosis via the p38 MAPK and JNK Signaling Pathways.
GADD45B Promotes Glucose-Induced Renal Tubular Epithelial-Mesenchymal Transition and Apoptosis via the p38 MAPK and JNK Signaling Pathways.
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DOI：
10.3389/fphys.2020.01074
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发表时间：
2020
影响因子：
4
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Xue M;Sun H;Xu R;Wang Y;Guo J;Li X;Cheng Y;Xu C;Tang C;Sun B;Chen L
生长停滞和DNA损伤诱导的β(GADD45B)与细胞周期停滞、DNA修复、细胞存活或应激反应中的细胞凋亡密切相关，并调节丝裂原活化蛋白激酶(MAPK)途径。在这里，我们使用RNA测序的方法，我们发现GADD45B在糖尿病肾脏中显著上调，伴随着肾小管上皮-间充质转化(EMT)和细胞凋亡，以及MAPK通路的激活。体外培养的人肾近端小管上皮细胞(HK-2细胞)中GADD45B的表达也被高糖(HG)刺激。此外，在HK-2细胞中过表达GADD45B加剧了肾小管上皮细胞的EMT和细胞凋亡，并增加了p38MAPK和c-Jun氨基末端激酶(JNK)的活性，而GADD45B的过表达则逆转了这些变化。值得注意的是，细胞外调节激酶(ERK)的活性不受GADD45B表达的影响。此外，p38MAPK(SB203580)和JNK(SP600125)的抑制剂可减轻HG-和GADD45B过表达诱导的肾小管上皮-间充质转化和细胞凋亡。提示GADD45B可能通过p38MAPK和JNK途径参与糖尿病肾小管上皮细胞的EMT和细胞凋亡，这可能是糖尿病肾损伤的重要机制之一。
Growth arrest and DNA damage-inducible beta (GADD45B) is closely linked with cell cycle arrest, DNA repair, cell survival, or apoptosis in response to stress and is known to regulate the mitogen-activated protein kinase (MAPK) pathway. Here, using an RNA sequencing approach, we determined that GADD45B was significantly upregulated in diabetic kidneys, which was accompanied by renal tubular epithelial-mesenchymal transition (EMT) and apoptosis, as well as elevated MAPK pathway activation. In vitro, GADD45B expression in cultured human kidney proximal tubular epithelial cells (HK-2 cells) was also stimulated by high glucose (HG). In addition, overexpression of GADD45B in HK-2 cells exacerbated renal tubular EMT and apoptosis and increased p38 MAPK and c-Jun N-terminal kinases (JNK) activation, whereas knockdown of GADD45B reversed these changes. Notably, the activity of extracellular regulated kinase (ERK) was not affected by GADD45B expression. Furthermore, inhibitors of p38 MAPK (SB203580) and JNK (SP600125) alleviated HG‐ and GADD45B overexpression-induced renal tubular epithelial-mesenchymal transition and apoptosis. These findings indicate a role of GADD45B in diabetes-induced renal tubular EMT and apoptosis via the p38 MAPK and JNK pathways, which may be an important mechanism of diabetic kidney injury.
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影响因子：
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作者：
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