期刊
ONCOTARGET
卷 8, 期 53, 页码 91185-91198出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.20434
关键词
diabetic nephropathy; SOCS2; renal injury; TLR4/NF-T beta pathway; inflammatory cytokines
Suppressor of cytokine signaling 2 (SOCS2) was reported to be involved in the development of Diabetic Nephropathy (DN). However, its underlying mechanism remains undefined. Western blot was carried out to determine the expressions of SOCS2, Toll-like receptors 4 (TLR4) and nuclear factor kappa B (NF-kappa B) pathway-related proteins in DN patients, streptozotocin (STZ)-induced DN rats and high glucose (HG)-stimulated podocytes. The effects of SOCS2 overexpression on renal injury, the inflammatory cytokines production, renal pathological changes, apoptosis and the TLR4/ NF-kappa B pathway in DN rats or HG-stimulated podocytes were investigated. TLR4 antagonist TAK-242 and NF-kappa B inhibitor PDTC were used to confirm the functional mechanism of SOCS2 overexpression in HG-stimulated podocytes. SOCS2 was down-regulated, while TLR4 and NF-kappa B were up-regulated in renal tissues of DN patients and DN rats. Ad-SOCS2 infection alleviated STZ-induced renal injury and pathological changes and inhibited STZ-induced IL-6, IL-1 beta and MCP-1 generation and activation of the TLR4/ NF-kappa B pathway in DN rats. SOCS2 overexpression attenuated apoptosis, suppressed the inflammatory cytokines expression, and inactivated the TLR4/ NF-kappa B pathway in HG-stimulated podocytes. Suppression of the TLR4/ NF-kappa B pathway enhanced the inhibitory effect of SOCS2 overexpression on apoptosis and inflammatory cytokines expressions in HG-stimulated podocytes. SOCS2 overexpression alleviated the development of DN by inhibiting the TLR4/ NF-kappa B pathway, contributing to developing new therapeutic strategies against DN.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据