Li Yongxia, Wang Wenzhe, Liu Changxuan, Zeng Min, Xu Li, Du Rong, Wang Cheng
Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Nephrology, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan 430022, China.
Biomedicines. 2023 Dec 25;12(1):51. doi: 10.3390/biomedicines12010051.
Renal inflammation and fibrosis are the important pathological phenomena associated with obstructive nephropathy. However, the underlying mechanism associated with this disease has yet to be fully elucidated. The present study, therefore, aimed to investigate the effects mediated by C1q/tumor necrosis factor-related protein 13 (CTRP13) on renal inflammation and fibrosis in addition to elucidating the underlying mechanism. To meet this aim, a mouse unilateral ureteral obstruction (UUO)-mediated renal dysfunction model was established. In addition, hematoxylin-eosin staining (H&E) staining and immunofluorescence experiments as well as Western blotting and reverse transcription quantitative (RT q) PCR analyses were performed. Recombinant CTRP13 was used to investigate the role of CTRP13 in chronic renal inflammation and fibrosis. A decreased expression level of CTRP13 was identified in the plasma of patients with renal fibrosis and in UUO-model mice. The renal histopathological and functional analyses revealed that CTRP13 could both reverse UUO mediated renal dysfunction and ameliorate the conditions of tubulointerstitial fibrosis and tubular injury. Additionally, CTRP13 was found to inhibit the expression levels of extracellular matrix proteins and proinflammatory mediators. In terms of the underlying mechanism, the protective effects on inflammation and fibrosis of the kidneys of CTRP13-treated mice undergoing UUO were found to be associated with the inactivation of the TGF β/Smad and NF κB p65 signaling pathways. Taken together, these findings have suggested that CTRP13 fulfills a vital role in the progression of obstructive nephropathy, thereby uncovering brand new insights into possible leads for the therapeutic treatment of chronic kidney disease (CKD).
肾脏炎症和纤维化是与梗阻性肾病相关的重要病理现象。然而，该疾病的潜在机制尚未完全阐明。因此，本研究旨在探讨C1q/肿瘤坏死因子相关蛋白13（CTRP13）对肾脏炎症和纤维化的影响，并阐明其潜在机制。为实现这一目标，建立了小鼠单侧输尿管梗阻（UUO）介导的肾功能障碍模型。此外，还进行了苏木精-伊红染色（H&E）、免疫荧光实验以及蛋白质免疫印迹和逆转录定量（RT-q）PCR分析。使用重组CTRP13来研究CTRP13在慢性肾脏炎症和纤维化中的作用。在肾纤维化患者的血浆和UUO模型小鼠中，CTRP13的表达水平降低。肾脏组织病理学和功能分析表明，CTRP13既可以逆转UUO介导的肾功能障碍，又可以改善肾小管间质纤维化和肾小管损伤的状况。此外，还发现CTRP13可抑制细胞外基质蛋白和促炎介质的表达水平。就潜在机制而言，发现CTRP13处理的UUO小鼠肾脏对炎症和纤维化的保护作用与TGF-β/Smad和NF-κB p65信号通路的失活有关。综上所述，这些发现表明CTRP13在梗阻性肾病的进展中起着至关重要的作用，从而为慢性肾脏病（CKD）的治疗提供了全新的思路。
