Zhang Xiuli, Liang Dan, Lian Xu, Chi Zhi-Hong, Wang Xuemei, Zhao Yue, Ping Zhang
Key Laboratory of Medical Cell Biology, Ministry of Education, Shenyang, Liaoning 110001, P.R. China.
Troops of 95935 Unit, Harbin, Heilongjiang 150111, P.R. China.
Mol Med Rep. 2016 Dec;14(6):5245-5252. doi: 10.3892/mmr.2016.5870. Epub 2016 Oct 20.
There is emerging evidence that tubulointerstitial fibrosis is the final common pathway of the majority of chronic progressive renal diseases, including diabetic nephropathy (DN). Zinc, an essential dietary element, has been suggested to be important for a number of protein functions during fibrosis in vivo and in vitro. However, the effect of zinc deficiency (ZnD) on renal interstitial fibrosis in DN remains unclear. The present study investigated the effect and the underlying mechanisms of ZnD on renal interstitial fibrosis during DN using an streptozotocin‑induced model of diabetes with immunofluorescence staining and western blot analysis. The present study identified that dietary zinc restriction significantly decreased zinc concentrations in the plasma and mouse kidney. ZnD enhanced albuminuria and extracellular matrix protein expression, associated with diabetic renal interstitial fibrosis by activation of renal interstitial fibroblasts and regulation of the expression of fibrosis‑associated factors, which may be mediated by the activation of fibroblasts via the TGF‑β/Smad signaling pathway. The data indicates that ZnD serves an important role in the pathogenic mechanisms of renal interstitial fibrosis during the development of DN.
越来越多的证据表明，肾小管间质纤维化是大多数慢性进行性肾脏疾病的最终共同途径，包括糖尿病肾病（DN）。锌作为一种必需的膳食元素，已被认为在体内和体外纤维化过程中对多种蛋白质功能具有重要作用。然而，锌缺乏（ZnD）对DN患者肾间质纤维化的影响仍不清楚。本研究使用链脲佐菌素诱导的糖尿病模型，通过免疫荧光染色和蛋白质印迹分析，研究了ZnD对DN期间肾间质纤维化的影响及其潜在机制。本研究发现，饮食中锌限制显著降低了血浆和小鼠肾脏中的锌浓度。ZnD通过激活肾间质成纤维细胞和调节纤维化相关因子的表达，增强蛋白尿和细胞外基质蛋白表达，这可能与糖尿病肾间质纤维化有关，其可能是通过TGF-β/Smad信号通路激活成纤维细胞介导的。数据表明，ZnD在DN发展过程中肾间质纤维化的发病机制中起重要作用。
