Wu Di, Bai Jiuxu, Cui Shaoyuan, Fu Bo, Yin Zhiwei, Cai Guangyan, Chen Xiangmei
Medical School of Chinese PLA, Beijing 100853, China.
Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853, China.
Ann Transl Med. 2020 Mar;8(6):355. doi: 10.21037/atm.2020.02.58.
Mesangial proliferative glomerulonephritis (MsPGN) is an epidemic disease with increasing occurrence. As important as mesangial cells, podocytes are key innate cells for MsPGN prognosis and recovery. Renal progenitor cells, located at the urinary pole (UP) of Bowman's capsule (BC), could alleviate kidney injury through their capacity to differentiate into podocytes.
Seventy-two male rats were categorized randomly into the sham (n=24), untreated Thy-1 (n=24) and losartan-treated (n=24) groups. We administered vehicle or losartan (50 mg/kg by gavage) daily to treat rats with anti-thy1.1 nephritis, an ideal model to simulate human MsPGN. Two weeks after the intravenous injection of antibody, urinary protein and blood samples were analyzed, pathological changes were examined, the number of podocytes was determined, and renal progenitor cells were studied.
Anti-thy1.1 nephritis was significantly alleviated after losartan treatment, as reported previously and as expected. Compared with the untreated Thy-1 group, the number of podocytes in the losartan group increased, and the area of renal progenitor cells significantly increased. The protein expression of components of the p-ERK pathway was determined during the development of renal progenitor cells differentiating into podocytes.
The data in this paper show the direct glomerular cell action of angiotensin II receptor blocker (ARB) treatment in improving outcomes in anti-thy1.1 nephritis. The positive effects of ARB medication on anti-thy1.1 nephritis were due to an increase in the number of renal epithelial progenitor cells (defined as PECs that expressed only stem cell markers without podocyte proteins).
系膜增生性肾小球肾炎(MsPGN)是一种发病率不断上升的流行病。足细胞与系膜细胞同样重要,是MsPGN预后和恢复的关键固有细胞。位于鲍曼囊(BC)尿极(UP)的肾祖细胞可通过分化为足细胞的能力来减轻肾损伤。
将72只雄性大鼠随机分为假手术组(n = 24)、未治疗的Thy-1组(n = 24)和氯沙坦治疗组(n = 24)。我们每天给予溶剂或氯沙坦(50 mg/kg灌胃)来治疗抗Thy1.1肾炎大鼠,这是一种模拟人类MsPGN的理想模型。静脉注射抗体两周后,分析尿蛋白和血液样本,检查病理变化,确定足细胞数量,并研究肾祖细胞。
如先前报道及预期,氯沙坦治疗后抗Thy1.1肾炎明显减轻。与未治疗的Thy-1组相比,氯沙坦组的足细胞数量增加,肾祖细胞面积显著增大。在肾祖细胞分化为足细胞的过程中,测定了p-ERK途径成分的蛋白表达。
本文数据显示血管紧张素II受体阻滞剂(ARB)治疗在改善抗Thy1.1肾炎预后方面对肾小球细胞有直接作用。ARB药物对抗Thy1.1肾炎的积极作用是由于肾上皮祖细胞数量增加(定义为仅表达干细胞标志物而无足细胞蛋白的PEC)。