Interleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.

Human umbilical cord Wharton's jelly derived mesenchymal stem cells (hUCMSCs), a source of cell therapy, have received a great deal of attention due to their homing or migrating ability in response to signals emanating from damaged sites. It has been found that IL-1β possesses the ability to in...

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Autores principales: Chun-Hao Chang, Yun-Li Lin, Yeu-Sheng Tyan, Yun-Hsuan Chiu, Ya-Han Liang, Chie-Pein Chen, Jiahn-Chun Wu, Hwai-Shi Wang
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/a360cb78a52640ac94e8c7662cf4f5de
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spelling oai:doaj.org-article:a360cb78a52640ac94e8c7662cf4f5de2021-12-02T20:11:16ZInterleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.1932-620310.1371/journal.pone.0252163https://doaj.org/article/a360cb78a52640ac94e8c7662cf4f5de2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252163https://doaj.org/toc/1932-6203Human umbilical cord Wharton's jelly derived mesenchymal stem cells (hUCMSCs), a source of cell therapy, have received a great deal of attention due to their homing or migrating ability in response to signals emanating from damaged sites. It has been found that IL-1β possesses the ability to induce the expression of matrix metalloproteinase-3 (MMP-3) in bone marrow MSCs. MMP-3 is involved in cell migration in various types of cells, including glioblastoma, vascular smooth muscle, and adult neural progenitor cells. In this study, we proposed that IL-1β influences hUCMSCs migration involving MMP-3. The expression level of MMP-3 in IL-1β-induced hUCMSCs was verified using cDNA microarray analysis, quantitative real-time PCR, ELISA and Western blot. Wound-healing and trans-well assay were used to investigate the cell migration and invasion ability of IL-1β-treated hUCMSCs. In addition, we pre-treated hUCMSCs with interleukin-1 receptor antagonist, MMP-3 inhibitors (ALX-260-165, UK 356618), or transfected with MMP-3 siRNA to confirm the role of MMP3 in IL-1β-induced cell migration. Our results showed that IL-1β induced MMP-3 expression is related to the migration of hUCMSCs. Moreover, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126, p38 inhibitor SB205380, JNK inhibitor SP600125 and Akt inhibitor GSK 690693 decreased IL-1β-induced MMP-3 mRNA and protein expression. The migration and invasion ability analyses showed that these inhibitors attenuated the IL-1β-induced migration and invasion ability of hUCMSCs. In conclusion, we have found that IL-1β induces the expression of MMP-3 through ERK1/2, JNK, p38 MAPK and Akt signaling pathways to enhance the migration of hUCMSCs. These results provide further understanding of the mechanisms in IL-1β-induced hUCMSCs migration to injury sites.Chun-Hao ChangYun-Li LinYeu-Sheng TyanYun-Hsuan ChiuYa-Han LiangChie-Pein ChenJiahn-Chun WuHwai-Shi WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0252163 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Chun-Hao Chang
Yun-Li Lin
Yeu-Sheng Tyan
Yun-Hsuan Chiu
Ya-Han Liang
Chie-Pein Chen
Jiahn-Chun Wu
Hwai-Shi Wang
Interleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.
description Human umbilical cord Wharton's jelly derived mesenchymal stem cells (hUCMSCs), a source of cell therapy, have received a great deal of attention due to their homing or migrating ability in response to signals emanating from damaged sites. It has been found that IL-1β possesses the ability to induce the expression of matrix metalloproteinase-3 (MMP-3) in bone marrow MSCs. MMP-3 is involved in cell migration in various types of cells, including glioblastoma, vascular smooth muscle, and adult neural progenitor cells. In this study, we proposed that IL-1β influences hUCMSCs migration involving MMP-3. The expression level of MMP-3 in IL-1β-induced hUCMSCs was verified using cDNA microarray analysis, quantitative real-time PCR, ELISA and Western blot. Wound-healing and trans-well assay were used to investigate the cell migration and invasion ability of IL-1β-treated hUCMSCs. In addition, we pre-treated hUCMSCs with interleukin-1 receptor antagonist, MMP-3 inhibitors (ALX-260-165, UK 356618), or transfected with MMP-3 siRNA to confirm the role of MMP3 in IL-1β-induced cell migration. Our results showed that IL-1β induced MMP-3 expression is related to the migration of hUCMSCs. Moreover, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126, p38 inhibitor SB205380, JNK inhibitor SP600125 and Akt inhibitor GSK 690693 decreased IL-1β-induced MMP-3 mRNA and protein expression. The migration and invasion ability analyses showed that these inhibitors attenuated the IL-1β-induced migration and invasion ability of hUCMSCs. In conclusion, we have found that IL-1β induces the expression of MMP-3 through ERK1/2, JNK, p38 MAPK and Akt signaling pathways to enhance the migration of hUCMSCs. These results provide further understanding of the mechanisms in IL-1β-induced hUCMSCs migration to injury sites.
format article
author Chun-Hao Chang
Yun-Li Lin
Yeu-Sheng Tyan
Yun-Hsuan Chiu
Ya-Han Liang
Chie-Pein Chen
Jiahn-Chun Wu
Hwai-Shi Wang
author_facet Chun-Hao Chang
Yun-Li Lin
Yeu-Sheng Tyan
Yun-Hsuan Chiu
Ya-Han Liang
Chie-Pein Chen
Jiahn-Chun Wu
Hwai-Shi Wang
author_sort Chun-Hao Chang
title Interleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.
title_short Interleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.
title_full Interleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.
title_fullStr Interleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.
title_full_unstemmed Interleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.
title_sort interleukin-1β-induced matrix metalloproteinase-3 via erk1/2 pathway to promote mesenchymal stem cell migration.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/a360cb78a52640ac94e8c7662cf4f5de
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