[High glucose regulates the expression of connective tissue growth factor and its receptor (low density lipoprotein receptor-related protein) in cultured podocytes].
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 (P< 0.05), began to decline on the 6th day, returned to the basal level on the 8th day (P>0.05). The levels of CTGF expression in normal glucose and mannitol glucose groups did not change markly. High glucose medium induced phosphorylation of ERK1/2 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 ERK1/2 was not detected in normal glucose and mannitol glucose groups. Blockade of phosphorylation of ERK1/2 with PD98059, a specific ERK1/2 activation inhibitor, 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.


CONCLUSIONS
Acute high glucose (2-4 days) stimulated the expression of CTGF protein via ERK1/2-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.
Li
Yong-qiang
YQ
Division of Nephrology, Peking University First Hospital, Beijing 100034, China.
Xiao
Yue-fei
YF
Huang
Hai-chang
HC
Li
Jing-zi
JZ
Yuan
Wei-zhong
WZ
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000096:biosynthesis*; D051379:Mice; D050199:Podocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D055513:Connective Tissue Growth Factor; D005947:Glucose