Feng Wenguang, Ying Wei-Zhong, Li Xingsheng, Curtis Lisa M, Sanders Paul W
Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.
Am J Physiol Renal Physiol. 2021 Jan 1;320(1):F87-F96. doi: 10.1152/ajprenal.00401.2020. Epub 2020 Dec 7.
Injured tubule epithelium stimulates a profibrotic milieu that accelerates loss of function in chronic kidney disease (CKD). This study tested the role of signal transducer and activator of transcription 1 (STAT1) in the progressive loss of kidney function in aristolochic acid (AA) nephropathy, a model of CKD. Mean serum creatinine concentration increased in wild-type (WT) littermates treated with AA, whereas mice were protected. Focal increases in the apical expression of kidney injury molecule (KIM)-1 were observed in the proximal tubules of WT mice with AA treatment but were absent in mice in the treatment group as well as in both control groups. A composite injury score, an indicator of proximal tubule injury, was reduced in mice treated with AA. Increased expression of integrin-β and phosphorylated Smad2/3 in proximal tubules as well as interstitial collagen and fibronectin were observed in WT mice following AA treatment but were all decreased in AA-treated mice. The data indicated that STAT1 activation facilitated the development of progressive kidney injury and interstitial fibrosis in AA nephropathy.
受损的肾小管上皮会刺激促纤维化环境，加速慢性肾脏病（CKD）的功能丧失。本研究检测了信号转导及转录激活因子1（STAT1）在马兜铃酸（AA）肾病（一种CKD模型）肾功能进行性丧失中的作用。用AA处理的野生型（WT）同窝小鼠血清肌酐平均浓度升高，而 小鼠受到保护。在接受AA处理的WT小鼠近端小管中观察到肾损伤分子（KIM）-1顶端表达的局灶性增加，但在处理组的 小鼠以及两个对照组中均未观察到。用AA处理的 小鼠的复合损伤评分（近端小管损伤的指标）降低。在接受AA处理的WT小鼠中，观察到近端小管中整合素-β和磷酸化Smad2/3的表达增加，以及间质胶原和纤连蛋白增加，但在接受AA处理的 小鼠中均降低。数据表明，STAT1激活促进了AA肾病中进行性肾损伤和间质纤维化的发展。
