IL-1β-Induced Matrix Metalloprotease-1 Promotes Mesenchymal Stem Cell Migration via PAR1 and G-Protein-Coupled Signaling Pathway

Mesenchymal stem cells (MSCs) are known for homing to sites of injury in response to signals of cellular damage. However, the mechanisms of how cytokines recruit stem cells to target tissue are still unclear. In this study, we found that the proinflammation cytokine interleukin-1β (IL-1β) promotes mesenchymal stem cell migration. The cDNA microarray data show that IL-1β induces matrix metalloproteinase-1 (MMP-1) expression. We then used quantitative real-time PCR and MMP-1 ELISA to verify the results. MMP-1 siRNA transfected MSCs, and MSC pretreatment with IL-1β inhibitor interleukin-1 receptor antagonist (IL-1RA), MMP tissue inhibitor of metalloproteinase 1 (TIMP1), tissue inhibitor of metalloproteinase 2 (TIMP2), MMP-1 inhibitor GM6001, and protease-activated receptor 1 (PAR1) inhibitor SCH79797 confirms that PAR1 protein signaling pathway leads to IL-1β-induced cell migration. In conclusion, IL-1β promotes the secretion of MMP-1, which then activates the PAR1 and G-protein-coupled signal pathways to promote mesenchymal stem cell migration.

Download Full-text

SCF/c-kit transactivates CXCR4-serine 339 phosphorylation through G protein-coupled receptor kinase 6 and regulates cardiac stem cell migration

Scientific Reports ◽

10.1038/srep26812 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 17

Author(s):

Ke Zuo ◽

Dong Kuang ◽

Ying Wang ◽

Yanli Xia ◽

Weilin Tong ◽

...

Keyword(s):

Stem Cell ◽

Cell Migration ◽

G Protein ◽

Cardiac Stem Cell ◽

Receptor Kinase ◽

G Protein Coupled Receptor ◽

Stem Cell Migration ◽

G Protein Coupled

Download Full-text

The mechanically activated p38/MMP-2 signaling pathway promotes bone marrow mesenchymal stem cell migration in rats

Archives of Oral Biology ◽

10.1016/j.archoralbio.2017.01.017 ◽

2017 ◽

Vol 76 ◽

pp. 55-60 ◽

Cited By ~ 7

Author(s):

Zihui Yang ◽

Baolei Wu ◽

Sen Jia ◽

Yinghua Zhao ◽

Rui Hou ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Cell Migration ◽

Mesenchymal Stem Cell ◽

Signaling Pathway ◽

Stem Cell Migration

Download Full-text

Interferon Gamma–treated Dental Pulp Stem Cells Promote Human Mesenchymal Stem Cell Migration In Vitro

Journal of Endodontics ◽

10.1016/j.joen.2015.02.018 ◽

2015 ◽

Vol 41 (8) ◽

pp. 1259-1264 ◽

Cited By ~ 15

Author(s):

Chelsee Strojny ◽

Michael Boyle ◽

Amelia Bartholomew ◽

Premanand Sundivakkam ◽

Satish Alapati

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Migration ◽

Mesenchymal Stem Cell ◽

Interferon Gamma ◽

Dental Pulp ◽

Human Mesenchymal Stem Cell ◽

Dental Pulp Stem Cells ◽

Stem Cell Migration

Download Full-text

G Protein-Coupled Receptor Kinase 3 Modulates Mesenchymal Stem Cell Proliferation and Differentiation Through Sphingosine-1-Phosphate Receptor Regulation

10.21203/rs.3.rs-310081/v1 ◽

2021 ◽

Author(s):

Jaime Brozowski ◽

Roman Timoshchenko ◽

Donald Stephen Serafin ◽

Brittney Allyn ◽

Jessica Koontz ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

G Protein ◽

Receptor Signaling ◽

Proliferation And Differentiation ◽

Sphingosine 1 Phosphate ◽

G Protein Coupled

Abstract Background The bone marrow niche supports hematopoietic cell development through intimate contact with multipotent stromal mesenchymal stem cells; however, the intracellular signaling, function, and regulation of such supportive niche cells are still being defined. Our study was designed to understand how G protein receptor kinase 3 (GRK3) affects bone marrow mesenchymal stem cell function by examining primary cells from GRK3-deficient mice, which we have previously published to have a hypercellular bone marrow and leukocytosis through negative regulation of CXCL12/CXCR4 signaling. Methods Murine GRK3-deficient bone marrow mesenchymal stromal cells were harvested and cultured to differentiate into three lineages (adipocyte, chondrocyte, and osteoblast) to confirm multi-potency and compared to wild type cells. Immunoblotting, modified-TANGO experiments, and flow cytometry were used to further examine the effects of GRK3 deficiency on bone marrow mesenchymal stromal cell receptor signaling. Microcomputed tomography was used to determine trabecular and cortical bone composition of GRK3-deficient mice and standard ELISA to quantitate CXCL12 production from cellular cultures.Results GRK3-deficient, bone marrow-derived mesenchymal stem cells exhibit enhanced and earlier osteogenic differentiation in vitro. The addition of a sphingosine kinase inhibitor abrogated the osteogenic proliferation and differentiation, suggesting sphingosine-1-phosphate receptor signaling was a putative G-protein coupled receptor regulated by GRK3. Immunoblotting showed prolonged ERK1/2 signaling after stimulation with sphingosine-1-phosphate in GRK3-deficient cells, and modified-TANGO assays suggested the involvement of β-arrestin-2 in sphingosine 1 phosphate receptor internalization. Conclusions Our work suggests that GRK3 regulates sphingosine-1-phosphate receptor signaling on bone marrow mesenchymal stem cells by recruiting β-arrestin to the occupied GPCR to promote internalization, and lack of such regulation affects mesenchymal stem cell functionality.

Download Full-text