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

Bu,Xiaolin; Bi,Xinling; Wang,Wuqing; Shi,Yuling; Hou,Qiang; Gu,Jun

doi:10.3892/mmr.2018.8567

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

Authors:
- Xiaolin Bu
- Xinling Bi
- Wuqing Wang
- Yuling Shi
- Qiang Hou
- Jun Gu
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Affiliations: Department of Dermatology, Gongli Hospital, The Second Military Medical University, Shanghai 200135, P.R. China, Department of Dermatology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China, Department of Dermatology, Central Hospital of Shanghai Minhang District, Shanghai 201100, P.R. China, Department of Dermatology, Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China, Department of Dermatology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China
Published online on: February 7, 2018 https://doi.org/10.3892/mmr.2018.8567
Pages: 5589-5594
Copyright: © Bu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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)‑α‑induced keratinocytes was downregulated by rhPTH (1‑34) in a dose‑dependent manner, compared with that in keratinocytes treated with TNF‑α 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.

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