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Article Open Access

Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice

  • Authors:
    • Zelin Lei
    • Xue Bai
    • Jianxiu Ma
    • Qin Yu
  • View Affiliations / Copyright

    Affiliations: Department of Respiration, Key Laboratory of Biotherapy and Regenerative Medicine, First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Medical College, Northwest Minzu University, Lanzhou, Gansu 730030, P.R. China
    Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1049-1056
    |
    Published online on: June 5, 2019
       https://doi.org/10.3892/mmr.2019.10341
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Abstract

Kisspeptin (KP) is an amidated neurohormone that is encoded by the KiSS‑1 metastasis suppressor (KISS1) gene and serves as the endogenous ligand for G protein‑coupled receptor 54 (GPR54). KP is involved in the regulation of several biological functions, such as reproduction, cancer and atherogenesis. Recent data suggested that KP may induce atherosclerotic plaque progression and instability, which may be reversed by the GPR54 antagonist KP‑234. Despite the KISS1 gene being previously reported as a downstream target of the classic transforming growth factor (TGF)/Smad2 signaling pathway, its role in fibrosis remains elusive. The purpose of the present study was to evaluate the role of KP‑13 (a product of the KISS1 gene) in a bleomycin (BLM)‑induced idiopathic pulmonary fibrosis model. Lung tissue samples were evaluated by quantitative PCR analysis, western blotting and ELISA. Daily intraperitoneal administration of KP‑13 significantly ameliorated body weight loss, histopathological lung abnormalities and pulmonary collagen deposition induced by BLM. Furthermore, KP‑13 downregulated the expression levels of tumor necrosis factor‑α, TGF‑β, collagen type I α1, actin α2 and matrix metalloproteinase 2 in BLM‑treated lungs compared with BLM group. Notably, the production of α‑smooth muscle actin in lung tissues, as well as the pulmonary levels of TGF‑β1 and phosphorylated‑Smad2/3, was reduced following treatment with KP‑13. The anti‑fibrotic effects of KP‑13 were reversed by KP‑234 (an antagonist of GPR54), but not by Cetrorelix (an antagonist of the gonadotropin‑releasing hormone receptor). Furthermore, apoptosis‑related proteins, such as Bax and caspase‑3, were decreased, whereas Bcl‑2 was markedly increased as determined by western blotting. Collectively, these data suggested that the KP/GPR54 signaling pathway may be a promising target for the treatment of idiopathic pulmonary fibrosis.
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Copy and paste a formatted citation
Spandidos Publications style
Lei Z, Bai X, Ma J and Yu Q: Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice. Mol Med Rep 20: 1049-1056, 2019.
APA
Lei, Z., Bai, X., Ma, J., & Yu, Q. (2019). Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice. Molecular Medicine Reports, 20, 1049-1056. https://doi.org/10.3892/mmr.2019.10341
MLA
Lei, Z., Bai, X., Ma, J., Yu, Q."Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice". Molecular Medicine Reports 20.2 (2019): 1049-1056.
Chicago
Lei, Z., Bai, X., Ma, J., Yu, Q."Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice". Molecular Medicine Reports 20, no. 2 (2019): 1049-1056. https://doi.org/10.3892/mmr.2019.10341
Copy and paste a formatted citation
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Spandidos Publications style
Lei Z, Bai X, Ma J and Yu Q: Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice. Mol Med Rep 20: 1049-1056, 2019.
APA
Lei, Z., Bai, X., Ma, J., & Yu, Q. (2019). Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice. Molecular Medicine Reports, 20, 1049-1056. https://doi.org/10.3892/mmr.2019.10341
MLA
Lei, Z., Bai, X., Ma, J., Yu, Q."Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice". Molecular Medicine Reports 20.2 (2019): 1049-1056.
Chicago
Lei, Z., Bai, X., Ma, J., Yu, Q."Kisspeptin‑13 inhibits bleomycin‑induced pulmonary fibrosis through GPR54 in mice". Molecular Medicine Reports 20, no. 2 (2019): 1049-1056. https://doi.org/10.3892/mmr.2019.10341
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