The knockout of nuclear factor E2 related factor and its effect on myofibroblast activation and renal fibrosis
CHENG Shuibing1, GUO Yangyang2, ZHU Hengyue2, XIAO Yanyi2, ZHENG Shizhang2, QI Ruyi2, ZHOU Junlei2, YANG Mei3, BAI Yongheng2
1.Department of Trauma Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 2.Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 3.Intensive Care Unit, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
CHENG Shuibing,GUO Yangyang,ZHU Hengyue, et al. The knockout of nuclear factor E2 related factor and its effect on myofibroblast activation and renal fibrosis[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2020, 50(4): 300-305，311.
Abstract：Objective: To investigate the knockout of nuclear factor E2 related factor (Nrf2) and its effect on the activation of renal myofibroblasts and interstitial fibrosis. Methods: Mice were randomly divided into four groups: Nrf2-wild-type sham group, Nrf2-knock-out sham group, Nrf2-wild-type unilateral ureteral obstruction (UUO) group and Nrf2-knock-out UUO group, with 6 mice in each group. The levels of serum creatinine and urea nitrogen were determined by biochemical analyzer; Periodic acid-Schiff staining (PAS) was used to observe the degree of renal damage; Masson staining was used to evaluate the accumulation of total collagen in renal interstitium; immunohistochemical staining was used to analyze the expression levels of myofibroblastic marker α-SMA, matrix component type III collagen and transforming growth factor β1 (TGF-β1); qRT-PCR was used to detect the mRNA expression of TGF-β1. Results: Compared with the Nrf2-wild-type sham group, the serum creatinine and urea nitrogen levels in the Nrf2-wild-type UUO group were significantly increased (P<0.05). There was no significant difference in serum creatinine and urea nitrogen levels between the Nrf2-wild-type UUO group and the Nrf2-knock-out UUO group (P>0.05). PAS staining showed that renal tissue damage was significantly aggravated in the Nrf2-knock-out UUO group (P<0.01), compared with the Nrf2-wild-type UUO group; Masson staining showed that total accumulation of renal interstitial collagen in the Nrf2-knock-out UUO group was significantly increased (P<0.01), compared with the Nrf2-wild-type UUO group; immunohistochemical staining showed that the expression of α-SMA and type III collagen in renal tissue of Nrf2-knock-out UUO group was significantly increased (P<0.05), compared with the Nrf2-wild-type UUO group, which was related to TGF-β1 mRNA and protein expression caused by Nrf2 knockout (P<0.05). Conclusion: Nrf2 knockout can aggravate the degree of renal injury and fibrosis caused by ureteral obstruction. Its mechanism may be related to Nrf2 knockout that increases TGF-β1 levels, resulting in excessive activation of myofibroblasts and collagen accumulation in renal interstitium.
