Chronic kidney disease (CKD) is one of the most common kidney diseases, and the most common pathological type of its outcome is renal interstitial fibrosis (RIF), whose etiology is still unclear. Roxadustat (FG4592), a prolyl-hydroxylase inhibitor (HIF-PHI) that targets hypoxia-inducible factors (HIF), is showing promise as a potential method to minimize damage to kidneys in the treatment of anemia associated with CKD; however, the mechanisms involved are not yet completely understood. The current study explored the protective effect of FG4592 pretreatment on the development of renal fibrosis. Combining the bioinformatics analysis, we proposed a new mechanism in which FG4592 can stabilize Hif-1 alpha expression, promote the levels of tight junction protein expression connexin43 (CX43), zonula occludens-1 (ZO-1), and adhesion junction molecule E-cadherin, thereby improving RIF and reducing inflammatory cytokine levels, restoring renal function. In addition, in vitro, FG4592 pretreatment can improve the transforming growth factor-beta (TGF-beta) induced human kidney-2 cells (HK-2) damage. In conclusion, the data from our investigation endorse the shielding influence of FG4592 on the folic acid (FA) induced renal dysfunction; Therefore, we consider FG4592 to be a promising therapeutic strategy for enhancing tubular epithelial cell repair and slowing the progression of renal fibrosis through the activation of the Gap Junction signaling pathway, which involves key proteins like CX43 and ZO-1.
[1]Shenyang Med Coll, Affiliated Cent Hosp, Dept Nephropathy, Shenyang 110075, Peoples R China.
[2]Third Hosp Jilin Univ, Dept Urol, Changchun 130031, Peoples R China.
[3]China Med Univ, Shengjing Hosp, Dept Nephropathy, Shenyang 110022, Peoples R China.
[4]China Med Univ, Shengjing Hosp, Dept Family Med, Shenyang 110022, Peoples R China.
[5]Naval Med Univ, Affiliated Hosp 3, Dept Rheumatol & Immunol, Shanghai 201805, Peoples R China.
[6]Shenyang Pharmaceut Univ, Dept Biol, Shenyang 110016, Peoples R China.
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