Wang Xinyao, Deng Zhenling, Wang Yue
Department of Nephrology, Peking University Third Hospital, Beijing, China.
Ren Fail. 2025 Dec;47(1):2458764. doi: 10.1080/0886022X.2025.2458764. Epub 2025 Feb 3.
Studies have reported that immunoglobulin G (IgG) "deposited" in the basement membrane of renal tubules is associated with tubulointerstitial damage in patients with diabetic kidney disease (DKD). Our previous study found that renal tubular epithelial cells (RTECs) can express and secrete IgG (RTEC-IgG) which may be associated with fibrosis. The present study aimed to explore the role of RTEC-IgG in renal tubulointerstitial fibrosis (TIF) in DKD. The results showed that RTEC-IgG expression was up-regulated in the renal tubulointerstitium of DKD patients and was associated with worse kidney function, more severe anemia, and higher interstitial fibrosis and tubular atrophy (IFTA) scores, and positively correlated with tubular epithelial mesenchymal transition (EMT) and TIF. IgG expression was also enhanced in the renal tubulointerstitium of DKD mice, which was positively correlated with TIF. High glucose induced an over expression of IgG in human renal tubular epithelial cells, and knockdown of IgG with siRNA relieved the expression of α-smooth muscle actin (SMA), collagen IV, fibronectin, and transforming growth factor (TGF)-β1 under high glucose conditions. In conclusion, our study suggests that RTEC-IgG is involved in the development of DKD by promoting EMT and interstitial fibrosis via TGF-β1.
研究报告称，糖尿病肾病（DKD）患者肾小管基底膜中“沉积”的免疫球蛋白G（IgG）与肾小管间质损伤有关。我们之前的研究发现，肾小管上皮细胞（RTECs）能够表达并分泌IgG（RTEC-IgG），这可能与纤维化有关。本研究旨在探讨RTEC-IgG在DKD患者肾小管间质纤维化（TIF）中的作用。结果显示，DKD患者肾小管间质中RTEC-IgG表达上调，且与肾功能较差、贫血更严重、间质纤维化和肾小管萎缩（IFTA）评分更高有关，并与肾小管上皮间质转化（EMT）和TIF呈正相关。在DKD小鼠的肾小管间质中，IgG表达也增强，且与TIF呈正相关。高糖诱导人肾小管上皮细胞中IgG过度表达，用小干扰RNA（siRNA）敲低IgG可缓解高糖条件下α平滑肌肌动蛋白（SMA）、IV型胶原、纤连蛋白和转化生长因子（TGF）-β1的表达。总之，我们的研究表明，RTEC-IgG通过TGF-β1促进EMT和间质纤维化，参与DKD的发展。
