ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress
Abstract Mesenchymal stem cells (MSCs) are known to facilitate angiogenesis and promote neo-vascularization via secretion of trophic factors. Here, we explored the molecular mechanism adopted by ADAMTS13 in modulating the expression of some key angiogenic markers in human umbilical cord-derived MSCs...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-51079-z |
| _version_ | 1797363273573597184 |
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| author | Srishti Dutta Gupta Malancha Ta |
| author_facet | Srishti Dutta Gupta Malancha Ta |
| author_sort | Srishti Dutta Gupta |
| collection | DOAJ |
| description | Abstract Mesenchymal stem cells (MSCs) are known to facilitate angiogenesis and promote neo-vascularization via secretion of trophic factors. Here, we explored the molecular mechanism adopted by ADAMTS13 in modulating the expression of some key angiogenic markers in human umbilical cord-derived MSCs under serum-deprivation stress. Wharton’s jelly MSCs (WJ-MSCs) were isolated from the perivascular region of human umbilical cords by explant culture. ADAMTS13 was upregulated at both mRNA and protein levels in WJ-MSCs under serum-deprivation stress. Correspondingly, some key angiogenic markers were also seen to be upregulated. By screening signaling pathways, p38 and JNK pathways were identified as negative and positive regulators for expression of ADAMTS13, and the angiogenic markers, respectively. Our results also indicated the Notch pathway and p53 as other probable partners modulating the expression of ADAMTS13 and the angiogenic markers. Knockdown of ADAMTS13 using siRNA led to reversal in the expression of these angiogenic markers. Further, ADAMTS13 was shown to act via the EphrinB2/EphB4 axis followed by ERK signaling to control expression of the angiogenic markers. Interestingly, stronger expression levels were noted for ADAMTS13, VEGF and PDGF under a more stringent nutrient stress condition. Thus, we highlight a novel role of ADAMTS13 in WJ-MSCs under nutrient stress condition. |
| first_indexed | 2024-03-08T16:18:59Z |
| format | Article |
| id | doaj.art-0334b8c64e56478497a8d6f79372f7ef |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T16:18:59Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0334b8c64e56478497a8d6f79372f7ef2024-01-07T12:27:17ZengNature PortfolioScientific Reports2045-23222024-01-0114112210.1038/s41598-023-51079-zADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stressSrishti Dutta Gupta0Malancha Ta1Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata (IISER Kolkata)Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata (IISER Kolkata)Abstract Mesenchymal stem cells (MSCs) are known to facilitate angiogenesis and promote neo-vascularization via secretion of trophic factors. Here, we explored the molecular mechanism adopted by ADAMTS13 in modulating the expression of some key angiogenic markers in human umbilical cord-derived MSCs under serum-deprivation stress. Wharton’s jelly MSCs (WJ-MSCs) were isolated from the perivascular region of human umbilical cords by explant culture. ADAMTS13 was upregulated at both mRNA and protein levels in WJ-MSCs under serum-deprivation stress. Correspondingly, some key angiogenic markers were also seen to be upregulated. By screening signaling pathways, p38 and JNK pathways were identified as negative and positive regulators for expression of ADAMTS13, and the angiogenic markers, respectively. Our results also indicated the Notch pathway and p53 as other probable partners modulating the expression of ADAMTS13 and the angiogenic markers. Knockdown of ADAMTS13 using siRNA led to reversal in the expression of these angiogenic markers. Further, ADAMTS13 was shown to act via the EphrinB2/EphB4 axis followed by ERK signaling to control expression of the angiogenic markers. Interestingly, stronger expression levels were noted for ADAMTS13, VEGF and PDGF under a more stringent nutrient stress condition. Thus, we highlight a novel role of ADAMTS13 in WJ-MSCs under nutrient stress condition.https://doi.org/10.1038/s41598-023-51079-z |
| spellingShingle | Srishti Dutta Gupta Malancha Ta ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress Scientific Reports |
| title | ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress |
| title_full | ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress |
| title_fullStr | ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress |
| title_full_unstemmed | ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress |
| title_short | ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress |
| title_sort | adamts13 regulates angiogenic markers via ephrin eph signaling in human mesenchymal stem cells under serum deprivation stress |
| url | https://doi.org/10.1038/s41598-023-51079-z |
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