（School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise 533000, China）

Abstract: The aim of this paper is to explore the mechanism of zinc-α2-glycoprotein (ZAG) forming a feedback pathway with extracellular signal- regulated kinase 1/2 (ERK1/2) and p38 to regulate epithelial mesenchymal transition (EMT) in rat renal epithelial cells (NRK-52E) induced by high uric acid environment, we divided NRK-52E into normal control group and high uric acid-induced group which was stimulated by 20 mg/dL uric acid for 48 h, and the cells in each group were transfected with overexpression of ZAG and knocked down respectively, to observe the interactions between ZAG expression level and ERK1/2 and p38 signaling pathways in the cells. The results revealed that the mRNA and protein expression of EMT-related molecules were elevated in rat kidney cells under high uric acid environment compared with the normal culture group (P<0.05); up-regulation of ZAG decreased the expression of mitogen-activated protein kinase kinase (MAPKK), ERK1/2, p38, activated transcription factor-2 (ATF2) and protein kinase B (PKB or Akt) mRNA in this pathway in rat kidney epithelial cells under high uric acid environment culture (P<0.01), while the downregulation of ZAG increased (P<0.05). At the protein level, the expression of MAPKK, p38 and Akt decreased in the ZAG up-regulated group compared to the untransfected group (P<0.05, P<0.01, P<0.001); and the expression of ERK1/2, p38 and Akt was elevated in the ZAG down-regulated group (P<0.001, P<0.05, P<0.01). The results suggest that transfection up-regulation of ZAG decreases the expression of laminin and vimentin mRNA, the marker genes related to EMT in NRK-52E; regulation of ZAG expression in NRK-52E can play a positive role in ERK1/2 and p38 signaling pathways, and thus inhibit renal cell EMT. This study provides an experimental basis for clinical treatment of hyperuricemic nephropathy (HN).

Key words: nephrofibrotic: epithelial mesenchymal transformation of urine; uric acid nephropathy; hyperuricemia; zinc-α2-glycoprotein

（Acta Laser Biology Sinica, 2024, 33(2): 176-184）