Mechanism of Tubular Epithelial Hypertrophy Induced by High Glucose / 中山大学学报(医学科学版)

ABSTRACT

[Objective]To study the mechanism of tubular epithelial hypertrophy induced by high glucose.[Methods]Human tubular epithelium line HK-2 cells were cultured in DMEM/F12 medium containing 1 g/L glucose(normal control group),4.5 g/L glacose(high slucose group),and 1 g/L glucose+3.5 g/L mannitol(iso-osmia control group),respectively.The cells of every group after cultured for 24 h,48 h.and 96 h were collected.The mRNA levels of CTGF and p27~(kip) were detected by real-time PCR.The protein levels of CTGF and p27~(kip) were detected by Western blot.The cellular proliferative activities were observed by MTT.The total cellular protein contents were detected by Bradford method.The cell cycle process was analyzed by flow cytometry.The cells of every group after being cultured for 30 win,1 h,24 h,and 48 h were collected.The levels of phospho-ERK1/2 were detected by Western blot.Every step was repeated for 3 times.[Results]High slucose could significantly up-regulate the mRNA and protein levels of CTGF and p27~(kip),activate ERK1/2 signal conductive pathway in HK-2 cells,make more cells arrest in G1 phase,decrease cellular proliferative activities,increase total cellular protein content reflecting cellular hypertrophy.[Conclusion]CTGF is an important mediator of tubular epithelial hypertrophy induced by high slucose.The mechanism is that CTGF up-regulates the p27~(kip) expression through activating ERK1/2 pathway.Up-regulated p27~(kip) lead proliferative cell to be arrested in G1 phase and cause cellular hypertrophy.