Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1‐phosphate in extravillous trophoblasts
Abstract Purpose Extracellular matrix remodeling is essential for extravillous trophoblast (EVT) cell migration and invasion during placental development and regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). Sphingosine kinases (SPHK1 and SPHK2) synthes...
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Reproductive Medicine and Biology |
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| Online Access: | https://doi.org/10.1002/rmb2.12379 |
| _version_ | 1828336604689727488 |
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| author | Kirti R. Chahar Vijay Kumar Phulwanti K. Sharma Daniela Brünnert Vibha Kaushik Pragya Gehlot Indu Shekhawat Suman Kumar Ajay Kumar Sharma Sandhya Kumari Pankaj Goyal |
| author_facet | Kirti R. Chahar Vijay Kumar Phulwanti K. Sharma Daniela Brünnert Vibha Kaushik Pragya Gehlot Indu Shekhawat Suman Kumar Ajay Kumar Sharma Sandhya Kumari Pankaj Goyal |
| author_sort | Kirti R. Chahar |
| collection | DOAJ |
| description | Abstract Purpose Extracellular matrix remodeling is essential for extravillous trophoblast (EVT) cell migration and invasion during placental development and regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). Sphingosine kinases (SPHK1 and SPHK2) synthesize sphingosine‐1‐phosphate (S1P), which works either intracellularly or extracellularly via its receptors S1PR1‐5 in an autocrine or paracrine manner. The role of SPHKs/S1P in regulating the expression of MMPs and TIMPs in EVT is mostly unknown and forms the primary objective of the study. Methods HTR‐8/SVneo cells were used as a model of EVT. To inhibit the expression of SPHKs, cells were treated with specific inhibitors, SK1‐I and SKI‐II, or gene‐specific siRNAs. The expressions of MMPs and TIMPs were estimated by qPCR. Results We demonstrated that SPHK1, MMP1‐3, and TIMP1‐3 were highly expressed in HTR‐8/SVneo cells. We found that treatment of cells with SK1‐I, SKI‐II, and knockdown of SPHK1 or SPHK2 increased the expression of MMP1, MMP3, and TIMP3. The addition of extracellular S1P inhibits the upregulation of MMPs and TIMPs in treated cells. Conclusions SPHKs negatively regulate the expression of MMP1, MMP3, and TIMP3. The level of intracellular S1P acts as a negative feedback switch for MMP1, MMP3, and TIMP3 expression in EVT cells. |
| first_indexed | 2024-04-13T22:03:06Z |
| format | Article |
| id | doaj.art-882e60852f184684a31524fc2fc74527 |
| institution | Directory Open Access Journal |
| issn | 1445-5781 1447-0578 |
| language | English |
| last_indexed | 2024-04-13T22:03:06Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Reproductive Medicine and Biology |
| spelling | doaj.art-882e60852f184684a31524fc2fc745272022-12-22T02:28:01ZengWileyReproductive Medicine and Biology1445-57811447-05782021-07-0120326727610.1002/rmb2.12379Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1‐phosphate in extravillous trophoblastsKirti R. Chahar0Vijay Kumar1Phulwanti K. Sharma2Daniela Brünnert3Vibha Kaushik4Pragya Gehlot5Indu Shekhawat6Suman Kumar7Ajay Kumar Sharma8Sandhya Kumari9Pankaj Goyal10Department of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer IndiaDepartment of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer IndiaDepartment of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer IndiaComprehensive Cancer Center Mainfranken Translational Oncology University Hospital of Würzburg Würzburg GermanyDepartment of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer IndiaDepartment of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer IndiaDepartment of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer IndiaDepartment of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer IndiaDepartment of Obstetrics & Gynecology J. L. N. Medical College Ajmer IndiaDepartment of Obstetrics & Gynecology J. L. N. Medical College Ajmer IndiaDepartment of Biotechnology School of Life Sciences Central University of Rajasthan Ajmer IndiaAbstract Purpose Extracellular matrix remodeling is essential for extravillous trophoblast (EVT) cell migration and invasion during placental development and regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). Sphingosine kinases (SPHK1 and SPHK2) synthesize sphingosine‐1‐phosphate (S1P), which works either intracellularly or extracellularly via its receptors S1PR1‐5 in an autocrine or paracrine manner. The role of SPHKs/S1P in regulating the expression of MMPs and TIMPs in EVT is mostly unknown and forms the primary objective of the study. Methods HTR‐8/SVneo cells were used as a model of EVT. To inhibit the expression of SPHKs, cells were treated with specific inhibitors, SK1‐I and SKI‐II, or gene‐specific siRNAs. The expressions of MMPs and TIMPs were estimated by qPCR. Results We demonstrated that SPHK1, MMP1‐3, and TIMP1‐3 were highly expressed in HTR‐8/SVneo cells. We found that treatment of cells with SK1‐I, SKI‐II, and knockdown of SPHK1 or SPHK2 increased the expression of MMP1, MMP3, and TIMP3. The addition of extracellular S1P inhibits the upregulation of MMPs and TIMPs in treated cells. Conclusions SPHKs negatively regulate the expression of MMP1, MMP3, and TIMP3. The level of intracellular S1P acts as a negative feedback switch for MMP1, MMP3, and TIMP3 expression in EVT cells.https://doi.org/10.1002/rmb2.12379extravillous trophoblastmatrix metalloproteinasesSphingosine 1‐phosphateSphingosine kinasetissue inhibitors of metalloproteases |
| spellingShingle | Kirti R. Chahar Vijay Kumar Phulwanti K. Sharma Daniela Brünnert Vibha Kaushik Pragya Gehlot Indu Shekhawat Suman Kumar Ajay Kumar Sharma Sandhya Kumari Pankaj Goyal Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1‐phosphate in extravillous trophoblasts Reproductive Medicine and Biology extravillous trophoblast matrix metalloproteinases Sphingosine 1‐phosphate Sphingosine kinase tissue inhibitors of metalloproteases |
| title | Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1‐phosphate in extravillous trophoblasts |
| title_full | Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1‐phosphate in extravillous trophoblasts |
| title_fullStr | Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1‐phosphate in extravillous trophoblasts |
| title_full_unstemmed | Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1‐phosphate in extravillous trophoblasts |
| title_short | Sphingosine kinases negatively regulate the expression of matrix metalloproteases (MMP1 and MMP3) and their inhibitor TIMP3 genes via sphingosine 1‐phosphate in extravillous trophoblasts |
| title_sort | sphingosine kinases negatively regulate the expression of matrix metalloproteases mmp1 and mmp3 and their inhibitor timp3 genes via sphingosine 1 phosphate in extravillous trophoblasts |
| topic | extravillous trophoblast matrix metalloproteinases Sphingosine 1‐phosphate Sphingosine kinase tissue inhibitors of metalloproteases |
| url | https://doi.org/10.1002/rmb2.12379 |
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