LMX1B positively regulates the expression of PHB1 in hypoxia-induced renal tubular epithelial cell injury

Abstract

Background and objective: Renal interstitial fibrosis (RIF) is a common pathological feature ofvarious chronic kidney diseases that progress to end-stage renal failure. The LMX1B gene plays animportant role in embryonic development, an important factor in regulating kidney development andmaintaining podocyte function. In the present study, we aimed to explore whether LMX1B regulatesPHB levels in the progression of RIF.Methods: A hypoxic/reoxygenation model in renal tubular epithelial cells (RTECs) was used tosimulate chronic injury in obstructive renal disease. Subcellular localization of LMX1B and prohibitin(PHB) 1 was observed using confocal laser microscopy. ROS and MDA levels were measured accordingto the reagent test kit protocols. The expression of LMX1B, PHB1, PHB2, TGF-β1, Col-IV, and FN wastested by western blotting, and the gray value of the band was analyzed using Image J.Results: LMX1B and PHB1 were both located in the nucleus of RTECs. The levels of PHB1 andPHB2 were closely associated with LMX1B levels. Overexpression of LMX1B in RTECs significantlyincreased the expression of PHB1 after H/R treatment. Moreover, the expression of TGF-β1, Col-IV,and FN was significantly decreased in RTECs infected with LMX1B lentiviral activation particles thanin control lentiviral activation-particle-infected RTECs. PHB1 levels were significantly decreased inLMX1B shRNA-transfected RTECs compared to control shRNA-transfected cells. Additionally, LMX1Boverexpression effectively inhibited hypoxia/reoxygenation (H/R)-induced ROS and MDA levels.Conclusion: The results demonstrated that LMX1B and PHB1 colocalized in the nucleus of RTECs,and LMX1B positively regulated PHB1 in an RTEC model system under H/R conditions. It plays aprotective role in hypoxic RTECs and inhibits RIF caused by RTEC injury