Effects of recombinant human parathyroid hormone (1-34) on cell proliferation, chemokine expression and the Hedgehog pathway in keratinocytes

摘要

Psoriasis is an autoimmune disease involving the excessive proliferation of keratinocytes mediated by T-cells. Parathyroid hormone (PTH) has been identified as an essential factor in the treatment of psoriasis. In the present study, the mechanism underlying the effect of recombinant human parathyroid hormone (rhPTH) (1-34) in keratinocytes was investigated. The effects of rhPTH (1-34) on cell proliferation, cell cycle, and the secretion and expression of C-X-C motif chemokine 11 (CXCL11) and components of the Hedgehog signaling pathway were examined in HaCaT cells by MTT assay, flow cytometric analysis, ELISA and gene chip analysis. The data showed that rhPTH (1-34) significantly inhibited keratinocyte proliferation at concentrations 8x10(-7) mol/l. rhPTH (1-34) induced G1 phase arrest of the cell cycle in the keratinocytes. The secretion of CXCL11 in tumor necrosis factor (TNF)--induced keratinocytes was downregulated by rhPTH (1-34) in a dose-dependent manner, compared with that in keratinocytes treated with TNF- alone. It was also found that rhPTH (1-34) inhibited the expression of CXCL11 in the HaCaT cells. rhPTH (1-34) also affected the Hedgehog signaling pathway specifically by regulating the expression of associated genes. In conclusion, these data suggested that rhPTH (1-34) inhibited cell proliferation, and the secretion and expression of CXCL11 in HaCaTs. rhPTH (1-34) also altered the expression of associated genes in the Hedgehog pathway. Therefore, rhPTH (1-34) can be considered as a novel therapeutic agent for the treatment of psoriasis.