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Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts
BACKGROUND: Fibroblasts activation-induced fibrosis can cause idiopathic pulmonary fibrosis (IPF). Excessive activation of fibroblasts contributes to poor healing or severe visceral fibrosis and even organ dysfunction. Sitagliptin acts as a dipeptidyl peptidase 4 inhibitor to reduce glucose level in...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Scientific Literature, Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191949/ https://www.ncbi.nlm.nih.gov/pubmed/32301442 http://dx.doi.org/10.12659/MSM.922644 |
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author | Liu, Xiuwu Zhang, Tao Zhang, Chengcai |
author_facet | Liu, Xiuwu Zhang, Tao Zhang, Chengcai |
author_sort | Liu, Xiuwu |
collection | PubMed |
description | BACKGROUND: Fibroblasts activation-induced fibrosis can cause idiopathic pulmonary fibrosis (IPF). Excessive activation of fibroblasts contributes to poor healing or severe visceral fibrosis and even organ dysfunction. Sitagliptin acts as a dipeptidyl peptidase 4 inhibitor to reduce glucose level in type 2 diabetes, but its role in fibrosis of lung fibroblasts is elusive. We investigated the mechanism of sitagliptin in TGF-β-activated lung fibroblasts and evaluated the efficacy of sitagliptin in extracellular matrix accumulation and fibroblasts proliferation. MATERIAL/METHODS: By in vitro lung fibroblasts culture, we assessed the expression of lung fibroblasts biomarker (α-SMA) and extracellular matrix (Col-1, Col-3, fibronectin) following TGF-β stimulation and treatment with sitagliptin. Mechanistically, the phosphorylation level of Smad-3 protein in cells was analyzed using Western blotting, and the apoptosis level was assessed by Western blotting and flow cytometry. The degree of proliferation was determined using immunofluorescence and scratch-healing assay. RESULTS: We found that treatment with sitagliptin attenuates fibroblasts activation following TGF-β stimulation. Furthermore, the extracellular matrix was decreased by sitagliptin treatment by suppressing the phosphorylation level of Smad-3 protein. We found that sitagliptin does not affect apoptosis in fibroblasts, but it does affect the degree of proliferation of lung fibroblasts, thus ameliorating fibrosis after TGF-β stimulation. CONCLUSIONS: Sitagliptin inhibits fibrosis in TGF-β-induced lung fibroblasts activation, which restrains extracellular matrix formation and cell proliferation in fibroblasts. Therefore, sitagliptin appears to have promise as a treatment of fibroproliferative disease caused by activation and proliferation of fibroblasts. |
format | Online Article Text |
id | pubmed-7191949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | International Scientific Literature, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71919492020-05-04 Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts Liu, Xiuwu Zhang, Tao Zhang, Chengcai Med Sci Monit Lab/In Vitro Research BACKGROUND: Fibroblasts activation-induced fibrosis can cause idiopathic pulmonary fibrosis (IPF). Excessive activation of fibroblasts contributes to poor healing or severe visceral fibrosis and even organ dysfunction. Sitagliptin acts as a dipeptidyl peptidase 4 inhibitor to reduce glucose level in type 2 diabetes, but its role in fibrosis of lung fibroblasts is elusive. We investigated the mechanism of sitagliptin in TGF-β-activated lung fibroblasts and evaluated the efficacy of sitagliptin in extracellular matrix accumulation and fibroblasts proliferation. MATERIAL/METHODS: By in vitro lung fibroblasts culture, we assessed the expression of lung fibroblasts biomarker (α-SMA) and extracellular matrix (Col-1, Col-3, fibronectin) following TGF-β stimulation and treatment with sitagliptin. Mechanistically, the phosphorylation level of Smad-3 protein in cells was analyzed using Western blotting, and the apoptosis level was assessed by Western blotting and flow cytometry. The degree of proliferation was determined using immunofluorescence and scratch-healing assay. RESULTS: We found that treatment with sitagliptin attenuates fibroblasts activation following TGF-β stimulation. Furthermore, the extracellular matrix was decreased by sitagliptin treatment by suppressing the phosphorylation level of Smad-3 protein. We found that sitagliptin does not affect apoptosis in fibroblasts, but it does affect the degree of proliferation of lung fibroblasts, thus ameliorating fibrosis after TGF-β stimulation. CONCLUSIONS: Sitagliptin inhibits fibrosis in TGF-β-induced lung fibroblasts activation, which restrains extracellular matrix formation and cell proliferation in fibroblasts. Therefore, sitagliptin appears to have promise as a treatment of fibroproliferative disease caused by activation and proliferation of fibroblasts. International Scientific Literature, Inc. 2020-04-17 /pmc/articles/PMC7191949/ /pubmed/32301442 http://dx.doi.org/10.12659/MSM.922644 Text en © Med Sci Monit, 2020 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) |
spellingShingle | Lab/In Vitro Research Liu, Xiuwu Zhang, Tao Zhang, Chengcai Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts |
title | Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts |
title_full | Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts |
title_fullStr | Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts |
title_full_unstemmed | Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts |
title_short | Sitagliptin Inhibits Extracellular Matrix Accumulation and Proliferation in Lung Fibroblasts |
title_sort | sitagliptin inhibits extracellular matrix accumulation and proliferation in lung fibroblasts |
topic | Lab/In Vitro Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191949/ https://www.ncbi.nlm.nih.gov/pubmed/32301442 http://dx.doi.org/10.12659/MSM.922644 |
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