Parathyroid hormone-potentiated connective tissue growth factor expression in human renal proximal tubular cells through activating the MAPK and NF-kappaB signalling pathways.

BACKGROUND: Secondary hyperparathyroidism is a universal complication of chronic renal diseases. One of the pathological consequences of hyperparathyroidism is impairment of the renal interstitium and tubules. However, the molecular mechanism of renal tubular interstitial impairment induced by parathyroid hormone (PTH) remains unclear. Enhanced and prolonged expression of connective tissue growth factor (CTGF) has been associated with fibrosis and inflammation in the kidney. The purpose of this study was to investigate the effects of PTH on CTGF expression patterns in human proximal tubular cell line-HK-2 cells.

METHODS: We treated cells with various concentrations of PTH for the indicated periods of time in the presence or absence of the mitogen-activated protein kinase (MAPK) inhibitor (PD98059) or the NF-κB inhibitor (PDTC).

RESULTS: Quantitative real-time RT-PCR analysis revealed that PTH at a concentration of 10(-12)-10(-10) M increased the mRNA levels of CTGF, which was similar to the trends of CTGF protein levels detected by immunoblotting assay. Our data clearly show the ability of human proximal tubular HK-2 cells to produce CTGF after the treatment with PTH. In addition, we showed that PTH induced the phosphorylation of MAPK p42 and p44, and increased NF-κB-binding activities in the PTH-treated cells. Moreover, both PD98059 and PDTC inhibited the effect of PTH on the expression of CTGF, which strongly suggests that these pathways play important roles in the PTH-induced CTGF upregulation in renal tubular cells.

CONCLUSIONS: Our results indicated for the first time that PTH may enhance the expression of CTGF in human kidney proximal tubular cells, suggesting that PTH may play an important role in the fibrotic and inflammatory process that is a hallmark for progression of chronic kidney disease.