High glucose regulates the expression of connective tissue growth factor and its receptor(low density lipoprotein receptor-related protein) in cultured podocytes / 北京大学学报(医学版)

ABSTRACT

Objective:To observe the expression of connective tissue growth factor(CTGF) and its receptor-low density lipoprotein receptor-related protein (LRP), and the relevant signaling pathway for the regulation by long-term high glucose exposure in cultured podocytes. Methods:The effects of high glucose on the expression of CTGF and its receptor LRP were analyzed by western blotting. The activation of mitogen activated protein kinase ( MAPKS )signaling pathway by high glucose was also examined. Results: Basal levels of CTGF were observed in cultured mouse podocytes, the levels of CTGF protein were increased by high glucose medium groups on the 2nd day, reached the peak on the 4th day(P0.05).The levels of CTGF expression in normal glucose and mannitol glucose groups did not change markly. High glucose medium induced phosphorylation of ERK_ 1/2 at as early as minute 30, reached the peak at hour 6; maintained the activity at hours 12 and 24, and declined to the basal level at hour 48. However, phosphorylation of ERK_ 1/2 was not detected in normal glucose and mannitol glucose groups. Blockade of phosphorylation of ERK_ 1/2 with PD98059, a specific ERK_ 1/2 activation inhibitior, did decrease the high glucose-triggered expression of CTGF protein in 4 days. High glucose had no effect on the expression of LRP protein at each time point. Conclusion: Acute high glucose (2-4 days)stimulated the expression of CTGF protein via ERK_ 1/2-dependent signaling pathway in cultured podocytes, while cultured in high glucose for 6-8 days, the podocytes did not increase its CTGF level. Long-term high glucose had no effect on the expression of LRP in podocytes.