PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress.
PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress.
复制标题
PARK7 通过诱导 SOD2 减少氧化应激来预防慢性肾损伤和肾纤维化
DOI：
10.3389/fimmu.2021.690697
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Dong Z
中科院分区：
文献类型：
--
作者：
Yin L;Li H;Liu Z;Wu W;Cai J;Tang C;Dong Z
无论病因如何，肾纤维化是慢性肾脏疾病的最终常见途径。帕金森病蛋白 7 (PARK7) 是一种参与多种细胞过程的多功能蛋白，但其在肾脏中的病理生理学作用仍然很大程度上未知。在这里，我们通过使用单侧输尿管梗阻（UUO）的体内小鼠模型和培养的肾近端肾小管细胞的转化生长因子-b（TGFB1）治疗的体外模型，确定了PARK7在肾纤维化中的作用，并进一步阐明了其潜在机制。 UUO 小鼠萎缩肾小管中 PARK7 显着减少，Park7 缺乏加剧了 UUO 诱导的肾纤维化、肾小管细胞凋亡、ROS 产生和炎症。在体外，TGFB1 治疗诱导肾小管细胞纤维化变化，并伴有 PARK7 的改变。 Park7 敲低加剧了 TGFB1 诱导的纤维化变化、细胞凋亡和 ROS 产生，而 Park7 过表达或用 ND-13（一种 PARK7 衍生肽）治疗则减弱了这些 TGFB1 诱导的变化。从机制上讲，在 TGFB1 处理或 UUO 处理后，PARK7 易位到肾小管细胞核中，诱导 SOD2（一种抗氧化酶）的表达。综上所述，这些结果表明 PARK7 通过诱导 SOD2 减少肾小管细胞的氧化应激，从而预防慢性肾损伤和肾纤维化。
Renal fibrosis is the final common pathway to chronic kidney diseases regardless of etiology. Parkinson disease protein 7 (PARK7) is a multifunctional protein involved in various cellular processes, but its pathophysiological role in kidneys remain largely unknown. Here, we have determined the role of PARK7 in renal fibrosis and have further elucidated the underlying mechanisms by using the in vivo mouse model of unilateral ureteric obstruction (UUO) and the in vitro model of transforming growth factor-b (TGFB1) treatment of cultured kidney proximal tubular cells. PARK7 decreased markedly in atrophic kidney tubules in UUO mice, and Park7 deficiency aggravated UUO-induced renal fibrosis, tubular cell apoptosis, ROS production and inflammation. In vitro, TGFB1 treatment induced fibrotic changes in renal tubular cells, which was accompanied by alterations of PARK7. Park7 knockdown exacerbated TGFB1-induced fibrotic changes, cell apoptosis and ROS production, whereas Park7 overexpression or treatment with ND-13 (a PARK7-derived peptide) attenuated these TGFB1-induced changes. Mechanistically, PARK7 translocated into the nucleus of renal tubular cells following TGFB1 treatment or UUO, where it induced the expression of SOD2, an antioxidant enzyme. Taken together, these results indicate that PARK7 protects against chronic kidney injury and renal fibrosis by inducing SOD2 to reduce oxidative stress in tubular cells.
登录
查看更多内容
影响因子：
5.6
作者：
De Miguel C;Kraus AC;Saludes MA;Konkalmatt P;Ruiz Domínguez A;Asico LD;Latham PS;Offen D;Jose PA;Cuevas S
通讯作者：
Cuevas S
影响因子：
7.4
作者：
Circu, Magdalena L.;Aw, Tak Yee
通讯作者：
Aw, Tak Yee
影响因子：
4.8
作者：
Honbou, K;Suzuki, NN;Inagaki, F
通讯作者：
Inagaki, F
DOI：
10.1073/pnas.0607260103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Clements, Casey M.;McNally, Richard S.;Ting, Jenny P-Y.
通讯作者：
Ting, Jenny P-Y.
影响因子：
--
作者：
Eltoweissy, Marwa;Mueller, Gerhard A.;Dihazi, Hassan
通讯作者：
Dihazi, Hassan