PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress

Abstract

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.

Single cell multi-omics of fibrotic kidney reveal epigenetic regulation of antioxidation and apoptosis within proximal tubule

“…In this paper, we found a deficiency in the antioxidant capacity of UUO or CIN kidney, previous research found UUO induction resulted in impaired renal function along with the downregulation of antioxidant proteins, such as NRF2, NQO1 and SOD, as a result, more ROS produced finally leads to oxidative stress and fibrosis [38,39]. While the expression of SOD2, an antioxidant enzyme, can protect against chronic kidney injury and renal fibrosis by reducing oxidative stress in renal tubular cells [40,41]. Peroxisome proliferator-activated receptors (PPARs) are a kind of transcription factor having anti-inflammatory effects, one study found the activation of PPAR-α by PPAR agonists can improve UUO phenotype [42].…”

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

“…After adaptive feeding for 7 days, 36 SPF male Sprague–Dawley rats (200 ± 20 g) were randomly divided into the following groups (n = 6 per group): Sham, Model, Losartan Potassium Tablets (LP), YSHXD low-, medium-, and high-dose; The rat model of RF was established using unilateral ureteral ligation (UUO) as previously described; 53 , 54 rats in the sham group underwent the same procedure but without ligation of disconnection of the ureter. The low-, medium- and high-dose YSHXD groups were administered (through gavage) oral doses of 3.94 g·kg −1 , 7.88 g·kg −1 and 15.75 g·kg −1 YSHXD (at a 1:1 ratio), respectively, based on the conversion of body surface area between rats and humans.…”

Effects of DJ‑1 on apoptosis and mitophagy of glomerular podocytes

“…Few previous studies have investigated how DJ-1 regulates the physiological function of glomerular podocytes ( 10 , 11 ). It has been suggested that autophagy activation and the inhibition of apoptosis have protective effects in high glucose-induced podocyte injury models, and that this protective effect is associated with DJ-1( 12 ).…”