Department of Endocrinology, Weinan Central Hospital, Weinan, Shaanxi, China.
Department of Infectious Diseases, Weinan Central Hospital, Weinan, Shaanxi, China.
J Cell Biochem. 2019 Apr;120(4):5729-5736. doi: 10.1002/jcb.27859. Epub 2018 Oct 26.
C1q/tumour necrosis factor-related protein-3 (CTRP3) is a member of CTRP family, and its blood level is reduced in human and rodent models of obesity and diabetes. However, the role of CTRP3 in diabetic nephropathy remains unclear. This study was designed to examine the effects of CTRP3 on cell proliferation and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) in response to high glucose (HG), and explore the potential molecular mechanisms. Our results demonstrated that the expression of CTRP3 was significantly decreased by HG stimulation in MCs. In addition, CTRP3 overexpression inhibited MCs proliferation, reactive oxygen species level, and ECM production in HG-stimulated MCs. Mechanistically, CTRP3 overexpression inhibited the activation of the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway in HG-stimulated MCs. Taken together, these findings indicated that CTRP3 attenuated HG-induced MC proliferation and ECM production through the inactivation of the JAK2/STAT3 signaling pathway. Thus, CTRP3 may be a potential therapeutic target for the treatment of diabetic nephropathy.
C1q/肿瘤坏死因子相关蛋白-3（CTRP3）是 CTRP 家族的一员，其在肥胖和糖尿病的人类和啮齿动物模型中的血液水平降低。然而，CTRP3 在糖尿病肾病中的作用尚不清楚。本研究旨在研究 CTRP3 对高糖（HG）刺激的人肾小球系膜细胞（MCs）中细胞增殖和细胞外基质（ECM）积累的影响，并探讨潜在的分子机制。我们的结果表明，HG 刺激显著降低了 MCs 中 CTRP3 的表达。此外，CTRP3 过表达抑制了 HG 刺激的 MCs 中 MCs 的增殖、活性氧水平和 ECM 产生。在机制上，CTRP3 过表达抑制了 HG 刺激的 MCs 中 Janus 激酶 2/信号转导和转录激活因子 3（JAK2/STAT3）通路的激活。总之，这些发现表明，CTRP3 通过失活 JAK2/STAT3 信号通路减轻 HG 诱导的 MC 增殖和 ECM 产生。因此，CTRP3 可能是治疗糖尿病肾病的潜在治疗靶点。
