PMID- 34019587 OWN - NLM STAT- MEDLINE DCOM- 20211026 LR - 20211026 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 16 IP - 5 DP - 2021 TI - Interleukin-1beta-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration. PG - e0252163 LID - 10.1371/journal.pone.0252163 [doi] LID - e0252163 AB - 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-1beta 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-1beta influences hUCMSCs migration involving MMP-3. The expression level of MMP-3 in IL-1beta-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-1beta-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-1beta-induced cell migration. Our results showed that IL-1beta 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-1beta-induced MMP-3 mRNA and protein expression. The migration and invasion ability analyses showed that these inhibitors attenuated the IL-1beta-induced migration and invasion ability of hUCMSCs. In conclusion, we have found that IL-1beta 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-1beta-induced hUCMSCs migration to injury sites. FAU - Chang, Chun-Hao AU - Chang CH AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Lin, Yun-Li AU - Lin YL AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Tyan, Yeu-Sheng AU - Tyan YS AD - Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC. FAU - Chiu, Yun-Hsuan AU - Chiu YH AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Liang, Ya-Han AU - Liang YH AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Chen, Chie-Pein AU - Chen CP AD - Division of High Risk Pregnancy, Mackay Memorial Hospital, Taipei, Taiwan, ROC. FAU - Wu, Jiahn-Chun AU - Wu JC AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Wang, Hwai-Shi AU - Wang HS AUID- ORCID: 0000-0003-1818-0970 AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210521 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Interleukin-1beta) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Blotting, Western MH - Cell Line MH - Cell Movement/drug effects MH - Flow Cytometry MH - Humans MH - Interleukin-1beta/*pharmacology MH - MAP Kinase Signaling System/*drug effects MH - Matrix Metalloproteinase 3/*metabolism MH - Mesenchymal Stem Cells/*drug effects/*metabolism MH - Signal Transduction/drug effects MH - Wound Healing/drug effects PMC - PMC8139494 COIS- The authors have declared that no competing interests exist. EDAT- 2021/05/22 06:00 MHDA- 2021/10/27 06:00 PMCR- 2021/05/21 CRDT- 2021/05/21 17:19 PHST- 2021/01/11 00:00 [received] PHST- 2021/05/11 00:00 [accepted] PHST- 2021/05/21 17:19 [entrez] PHST- 2021/05/22 06:00 [pubmed] PHST- 2021/10/27 06:00 [medline] PHST- 2021/05/21 00:00 [pmc-release] AID - PONE-D-21-01063 [pii] AID - 10.1371/journal.pone.0252163 [doi] PST - epublish SO - PLoS One. 2021 May 21;16(5):e0252163. doi: 10.1371/journal.pone.0252163. eCollection 2021.