Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin
Epidermal knockout of integrin β1 results in complete disorganization of the basement membrane (BM), resulting in neonatal lethality. Here, we report that this disorganization is exacerbated by an early embryonic inflammatory response involving the recruitment of tissue-resident and monocyte-derived...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716311433 |
| _version_ | 1830488672972046336 |
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| author | Ambika S. Kurbet Samarth Hegde Oindrila Bhattacharjee Srujan Marepally Praveen K. Vemula Srikala Raghavan |
| author_facet | Ambika S. Kurbet Samarth Hegde Oindrila Bhattacharjee Srujan Marepally Praveen K. Vemula Srikala Raghavan |
| author_sort | Ambika S. Kurbet |
| collection | DOAJ |
| description | Epidermal knockout of integrin β1 results in complete disorganization of the basement membrane (BM), resulting in neonatal lethality. Here, we report that this disorganization is exacerbated by an early embryonic inflammatory response involving the recruitment of tissue-resident and monocyte-derived macrophages to the dermal-epidermal junction, associated with increased matrix metalloproteinase activity. Remarkably, the skin barrier in the integrin β1 knockout animals is intact, suggesting that this inflammatory response is initiated in a sterile environment. We demonstrate that the molecular mechanism involves de novo expression of integrin αvβ6 in the basal epidermal cells, which activates a TGF-β1 driven inflammatory cascade resulting in upregulation of dermal NF-κB in a Tenascin C-dependent manner. Importantly, treatment of β1 KO embryos in utero with small molecule inhibitors of TGF-βR1 and NF-κB results in marked rescue of the BM defects and amelioration of immune response, revealing an unconventional immuno-protective role for integrin β1 during BM remodeling. |
| first_indexed | 2024-12-21T19:22:51Z |
| format | Article |
| id | doaj.art-5a0b2a2ae9254ea28a7a1c18c9d56330 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T19:22:51Z |
| publishDate | 2016-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5a0b2a2ae9254ea28a7a1c18c9d563302022-12-21T18:52:54ZengElsevierCell Reports2211-12472016-09-0116123334334710.1016/j.celrep.2016.08.062Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic SkinAmbika S. Kurbet0Samarth Hegde1Oindrila Bhattacharjee2Srujan Marepally3Praveen K. Vemula4Srikala Raghavan5Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK PO, Bellary Road, Bangalore 560065, IndiaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK PO, Bellary Road, Bangalore 560065, IndiaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK PO, Bellary Road, Bangalore 560065, IndiaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK PO, Bellary Road, Bangalore 560065, IndiaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK PO, Bellary Road, Bangalore 560065, IndiaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK PO, Bellary Road, Bangalore 560065, IndiaEpidermal knockout of integrin β1 results in complete disorganization of the basement membrane (BM), resulting in neonatal lethality. Here, we report that this disorganization is exacerbated by an early embryonic inflammatory response involving the recruitment of tissue-resident and monocyte-derived macrophages to the dermal-epidermal junction, associated with increased matrix metalloproteinase activity. Remarkably, the skin barrier in the integrin β1 knockout animals is intact, suggesting that this inflammatory response is initiated in a sterile environment. We demonstrate that the molecular mechanism involves de novo expression of integrin αvβ6 in the basal epidermal cells, which activates a TGF-β1 driven inflammatory cascade resulting in upregulation of dermal NF-κB in a Tenascin C-dependent manner. Importantly, treatment of β1 KO embryos in utero with small molecule inhibitors of TGF-βR1 and NF-κB results in marked rescue of the BM defects and amelioration of immune response, revealing an unconventional immuno-protective role for integrin β1 during BM remodeling.http://www.sciencedirect.com/science/article/pii/S2211124716311433 |
| spellingShingle | Ambika S. Kurbet Samarth Hegde Oindrila Bhattacharjee Srujan Marepally Praveen K. Vemula Srikala Raghavan Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin Cell Reports |
| title | Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin |
| title_full | Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin |
| title_fullStr | Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin |
| title_full_unstemmed | Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin |
| title_short | Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin |
| title_sort | sterile inflammation enhances ecm degradation in integrin β1 ko embryonic skin |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716311433 |
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