{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:29:11Z","timestamp":1793276951772,"version":"4.5.0"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although impaired keratinocyte migration is a recognized hallmark of chronic wounds, the molecular mechanisms underpinning impaired cell movement are poorly understood. Here, we demonstrate that both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) exhibit global deregulation of cytoskeletal organization in genomic comparison to normal skin and acute wounds. Interestingly, we found that DFUs and VLUs exhibited downregulation of ArhGAP35, which serves both as an inactivator of RhoA and as a glucocorticoid repressor. Since chronic wounds exhibit elevated levels of cortisol and caveolin-1 (Cav1), we posited that observed elevation of Cav1 expression may contribute to impaired actin-cytoskeletal signaling, manifesting in aberrant keratinocyte migration. We showed that Cav1 indeed antagonizes ArhGAP35, resulting in increased activation of RhoA and diminished activation of Cdc42, which can be rescued by Cav1 disruption. Furthermore, we demonstrate that both inducible keratinocyte specific Cav1 knockout mice, and M\u03b2CD treated diabetic mice, exhibit accelerated wound closure. Taken together, our findings provide a previously unreported mechanism by which Cav1-mediated cytoskeletal organization prevents wound closure in patients with chronic wounds.<\/jats:p>","DOI":"10.1038\/s42003-021-02298-5","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T06:03:33Z","timestamp":1623996213000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Glucocorticoid-mediated induction of caveolin-1 disrupts cytoskeletal organization, inhibits cell migration and re-epithelialization of non-healing wounds"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5114-9524","authenticated-orcid":false,"given":"Ivan","family":"Jozic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Abdo","family":"Abujamra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6307-7986","authenticated-orcid":false,"given":"Tongyu C.","family":"Wikramanayake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Marjanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka C.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheyanne R.","family":"Head","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0197-6198","authenticated-orcid":false,"given":"Irena","family":"Pastar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Kirsner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotios M.","family":"Andreopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Musi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-0193","authenticated-orcid":false,"given":"Marjana","family":"Tomic-Canic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"2298_CR1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1089\/wound.2019.1095","volume":"9","author":"RA Fayne","year":"2020","unstructured":"Fayne, R. A. et al. The potential impact of social genomics on wound healing. Adv. Wound Care 9, 325\u2013331 (2020).","journal-title":"Adv. Wound Care"},{"key":"2298_CR2","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1007\/s13671-018-0234-9","volume":"7","author":"S Ellis","year":"2018","unstructured":"Ellis, S., Lin, E. J. & Tartar, D. Immunology of wound healing. Curr. Dermatol Rep. 7, 350\u2013358 (2018).","journal-title":"Curr. Dermatol Rep."},{"key":"2298_CR3","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1089\/wound.2015.0635","volume":"4","author":"RG Frykberg","year":"2015","unstructured":"Frykberg, R. G. & Banks, J. Challenges in the treatment of chronic wounds. Adv. Wound Care 4, 560\u2013582 (2015).","journal-title":"Adv. Wound Care"},{"key":"2298_CR4","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1089\/wound.2019.0967","volume":"9","author":"S Li","year":"2020","unstructured":"Li, S. et al. Imaging in chronic wound diagnostics. Adv. Wound Care 9, 245\u2013263 (2020).","journal-title":"Adv. Wound Care"},{"key":"2298_CR5","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/wrr.12683","volume":"27","author":"M Olsson","year":"2019","unstructured":"Olsson, M. et al. The humanistic and economic burden of chronic wounds: a systematic review. Wound Repair Regen. 27, 114\u2013125 (2019).","journal-title":"Wound Repair Regen."},{"key":"2298_CR6","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1111\/j.1524-475X.2009.00543.x","volume":"17","author":"CK Sen","year":"2009","unstructured":"Sen, C. K. et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 17, 763\u2013771 (2009).","journal-title":"Wound Repair Regen."},{"key":"2298_CR7","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1038\/jid.2015.94","volume":"135","author":"RA Charafeddine","year":"2015","unstructured":"Charafeddine, R. A. et al. Fidgetin-like 2: a microtubule-based regulator of wound healing. J. Invest Dermatol 135, 2309\u20132318 (2015).","journal-title":"J. Invest Dermatol"},{"key":"2298_CR8","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1038\/jid.2015.237","volume":"135","author":"I Jozic","year":"2015","unstructured":"Jozic, I. et al. Nanoparticles for fidgety cell movement and enhanced wound healing. J. Invest Dermatol 135, 2151\u20132153 (2015).","journal-title":"J. Invest Dermatol"},{"key":"2298_CR9","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1126\/science.1092053","volume":"302","author":"AJ Ridley","year":"2003","unstructured":"Ridley, A. J. et al. Cell migration: integrating signals from front to back. Science 302, 1704\u20131709 (2003).","journal-title":"Science"},{"key":"2298_CR10","first-page":"233","volume":"65","author":"MP Sheetz","year":"1999","unstructured":"Sheetz, M. P. et al. Cell migration as a five-step cycle. Biochem Soc. Symp. 65, 233\u2013243 (1999).","journal-title":"Biochem Soc. Symp."},{"key":"2298_CR11","doi-asserted-by":"publisher","first-page":"265sr6","DOI":"10.1126\/scitranslmed.3009337","volume":"6","author":"SA Eming","year":"2014","unstructured":"Eming, S. A., Martin, P. & Tomic-Canic, M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med 6, 265sr6 (2014).","journal-title":"Sci. Transl. Med"},{"key":"2298_CR12","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1016\/j.ymthe.2019.07.016","volume":"27","author":"I Jozic","year":"2019","unstructured":"Jozic, I. et al. Pharmacological and genetic inhibition of caveolin-1 promotes epithelialization and wound closure. Mol. Ther. 27, 1992\u20132004 (2019).","journal-title":"Mol. Ther."},{"key":"2298_CR13","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/S0960-9822(99)80286-3","volume":"9","author":"K Rottner","year":"1999","unstructured":"Rottner, K., Hall, A. & Small, J. V. Interplay between Rac and Rho in the control of substrate contact dynamics. Curr. Biol. 9, 640\u2013648 (1999).","journal-title":"Curr. Biol."},{"key":"2298_CR14","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1083\/jcb.200701006","volume":"177","author":"A Grande-Garcia","year":"2007","unstructured":"Grande-Garcia, A. et al. Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases. J. Cell Biol. 177, 683\u2013694 (2007).","journal-title":"J. Cell Biol."},{"key":"2298_CR15","doi-asserted-by":"crossref","unstructured":"Sawaya, A. P. et al. Mevastatin promotes healing by targeting caveolin-1 to restore EGFR signaling. JCI Insight 4, e129320 (2019).","DOI":"10.1172\/jci.insight.129320"},{"key":"2298_CR16","doi-asserted-by":"publisher","first-page":"5343","DOI":"10.1167\/iovs.13-11955","volume":"54","author":"S Pothula","year":"2013","unstructured":"Pothula, S., Bazan, H. E. & Chandrasekher, G. Regulation of Cdc42 expression and signaling is critical for promoting corneal epithelial wound healing. Invest Ophthalmol. Vis. Sci. 54, 5343\u20135352 (2013).","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"2298_CR17","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/exd.14068","volume":"29","author":"AN Egger","year":"2020","unstructured":"Egger, A. N. et al. The importance of caveolins and caveolae to dermatology: lessons from the caves and beyond. Exp. Dermatol 29, 136\u2013148 (2020).","journal-title":"Exp. Dermatol"},{"key":"2298_CR18","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/S0169-409X(01)00139-9","volume":"49","author":"J Couet","year":"2001","unstructured":"Couet, J. et al. Cell biology of caveolae and caveolin. Adv. Drug Deliv. Rev. 49, 223\u2013235 (2001).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"2298_CR19","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1083\/jcb.126.1.111","volume":"126","author":"MP Lisanti","year":"1994","unstructured":"Lisanti, M. P. et al. Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease. J. Cell Biol. 126, 111\u2013126 (1994).","journal-title":"J. Cell Biol."},{"key":"2298_CR20","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41514-019-0034-x","volume":"5","author":"IL Kruglikov","year":"2019","unstructured":"Kruglikov, I. L. & Scherer, P. E. Caveolin-1 as a pathophysiological factor and target in psoriasis. NPJ Aging Mech. Dis. 5, 4 (2019).","journal-title":"NPJ Aging Mech. Dis."},{"key":"2298_CR21","doi-asserted-by":"publisher","first-page":"6525","DOI":"10.1074\/jbc.272.10.6525","volume":"272","author":"J Couet","year":"1997","unstructured":"Couet, J. et al. Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J. Biol. Chem. 272, 6525\u20136533 (1997).","journal-title":"J. Biol. Chem."},{"key":"2298_CR22","doi-asserted-by":"publisher","first-page":"5419","DOI":"10.1074\/jbc.273.10.5419","volume":"273","author":"T Okamoto","year":"1998","unstructured":"Okamoto, T. et al. Caveolins, a family of scaffolding proteins for organizing \u201cpreassembled signaling complexes\u201d at the plasma membrane. J. Biol. Chem. 273, 5419\u20135422 (1998).","journal-title":"J. Biol. Chem."},{"key":"2298_CR23","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1021\/acs.analchem.9b04542","volume":"92","author":"A Castellanos","year":"2020","unstructured":"Castellanos, A. et al. Multimodal, in situ imaging of ex vivo human skin reveals decrease of cholesterol sulfate in the neoepithelium during acute wound healing. Anal. Chem. 92, 1386\u20131394 (2020).","journal-title":"Anal. Chem."},{"key":"2298_CR24","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1016\/j.jid.2016.11.036","volume":"137","author":"I Jozic","year":"2017","unstructured":"Jozic, I. et al. Stress signals, mediated by membranous glucocorticoid receptor, activate PLC\/PKC\/GSK-3beta\/beta-catenin pathway to inhibit wound closure. J. Invest. Dermatol. 137, 1144\u20131154 (2017).","journal-title":"J. Invest. Dermatol."},{"key":"2298_CR25","doi-asserted-by":"publisher","first-page":"e0137133","DOI":"10.1371\/journal.pone.0137133","volume":"10","author":"HA Ramirez","year":"2015","unstructured":"Ramirez, H. A. et al. Comparative genomic, MicroRNA, and tissue analyses reveal subtle differences between non-diabetic and diabetic foot skin. PLoS One 10, e0137133 (2015).","journal-title":"PLoS One"},{"key":"2298_CR26","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/j.jid.2017.11.038","volume":"138","author":"HA Ramirez","year":"2018","unstructured":"Ramirez, H. A. et al. Staphylococcus aureus triggers induction of miR-15B-5P to diminish DNA repair and deregulate inflammatory response in diabetic foot ulcers. J. Invest. Dermatol. 138, 1187\u20131196 (2018).","journal-title":"J. Invest. Dermatol."},{"key":"2298_CR27","doi-asserted-by":"crossref","unstructured":"Stone, R. C. et al. A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers. Sci. Transl. Med. 9, eaaf8611 (2017).","DOI":"10.1126\/scitranslmed.aaf8611"},{"key":"2298_CR28","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1111\/wrr.12778","volume":"28","author":"RC Stone","year":"2020","unstructured":"Stone, R. C. et al. A bioengineered living cell construct activates metallothionein\/zinc\/MMP8 and inhibits TGFbeta to stimulate remodeling of fibrotic venous leg ulcers. Wound Repair Regen. 28, 164\u2013176 (2020).","journal-title":"Wound Repair Regen."},{"key":"2298_CR29","doi-asserted-by":"publisher","first-page":"5151","DOI":"10.1002\/j.1460-2075.1993.tb06210.x","volume":"12","author":"AJ Ridley","year":"1993","unstructured":"Ridley, A. J. et al. rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. EMBO J. 12, 5151\u20135160 (1993).","journal-title":"EMBO J."},{"key":"2298_CR30","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/S0171-9335(99)80019-3","volume":"78","author":"S Vincent","year":"1999","unstructured":"Vincent, S. & Settleman, J. Inhibition of RhoGAP activity is sufficient for the induction of Rho-mediated actin reorganization. Eur. J. Cell Biol. 78, 539\u2013548 (1999).","journal-title":"Eur. J. Cell Biol."},{"key":"2298_CR31","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1359\/JBMR.050113","volume":"20","author":"G Wang","year":"2005","unstructured":"Wang, G. & Beier, F. Rac1\/Cdc42 and RhoA GTPases antagonistically regulate chondrocyte proliferation, hypertrophy, and apoptosis. J. Bone Min. Res. 20, 1022\u20131031 (2005).","journal-title":"J. Bone Min. Res"},{"key":"2298_CR32","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1091\/mbc.e09-10-0859","volume":"22","author":"B Jackson","year":"2011","unstructured":"Jackson, B. et al. RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes. Mol. Biol. Cell 22, 593\u2013605 (2011).","journal-title":"Mol. Biol. Cell"},{"key":"2298_CR33","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1046\/j.1523-1747.2002.01736.x","volume":"118","author":"S Mazzalupo","year":"2002","unstructured":"Mazzalupo, S., Wawersik, M. J. & Coulombe, P. A. An ex vivo assay to assess the potential of skin keratinocytes for wound epithelialization. J. Invest Dermatol 118, 866\u2013870 (2002).","journal-title":"J. Invest Dermatol"},{"key":"2298_CR34","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1007\/s00109-008-0353-z","volume":"86","author":"A Harsha","year":"2008","unstructured":"Harsha, A. et al. ADAM12: a potential target for the treatment of chronic wounds. J. Mol. Med. 86, 961\u2013969 (2008).","journal-title":"J. Mol. Med."},{"key":"2298_CR35","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1111\/j.1067-1927.2004.12404.x","volume":"12","author":"RD Galiano","year":"2004","unstructured":"Galiano, R. D. et al. Quantitative and reproducible murine model of excisional wound healing. Wound Repair Regen. 12, 485\u2013492 (2004).","journal-title":"Wound Repair Regen."},{"key":"2298_CR36","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/j.jid.2017.01.024","volume":"137","author":"AT Slominski","year":"2017","unstructured":"Slominski, A. T. & Zmijewski, M. A. Glucocorticoids inhibit wound healing: novel mechanism of action. J. Invest. Dermatol. 137, 1012\u20131014 (2017).","journal-title":"J. Invest. Dermatol."},{"key":"2298_CR37","doi-asserted-by":"publisher","first-page":"e77107","DOI":"10.1371\/journal.pone.0077107","volume":"8","author":"A Hou","year":"2013","unstructured":"Hou, A. et al. Rho GTPases and regulation of cell migration and polarization in human corneal epithelial cells. PLoS One 8, e77107 (2013).","journal-title":"PLoS One"},{"key":"2298_CR38","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1038\/onc.2011.288","volume":"31","author":"E Arpaia","year":"2012","unstructured":"Arpaia, E. et al. The interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk. Oncogene 31, 884\u2013896 (2012).","journal-title":"Oncogene"},{"key":"2298_CR39","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.cardiores.2006.10.020","volume":"73","author":"C Dubroca","year":"2007","unstructured":"Dubroca, C. et al. RhoA activation and interaction with Caveolin-1 are critical for pressure-induced myogenic tone in rat mesenteric resistance arteries. Cardiovasc Res 73, 190\u2013197 (2007).","journal-title":"Cardiovasc Res"},{"key":"2298_CR40","doi-asserted-by":"publisher","first-page":"8210","DOI":"10.1158\/0008-5472.CAN-08-0343","volume":"68","author":"B Joshi","year":"2008","unstructured":"Joshi, B. et al. Phosphorylated caveolin-1 regulates Rho\/ROCK-dependent focal adhesion dynamics and tumor cell migration and invasion. Cancer Res. 68, 8210\u20138220 (2008).","journal-title":"Cancer Res."},{"key":"2298_CR41","doi-asserted-by":"publisher","first-page":"18961","DOI":"10.1074\/jbc.M603604200","volume":"281","author":"AK Nevins","year":"2006","unstructured":"Nevins, A. K. & Thurmond, D. C. Caveolin-1 functions as a novel Cdc42 guanine nucleotide dissociation inhibitor in pancreatic beta-cells. J. Biol. Chem. 281, 18961\u201318972 (2006).","journal-title":"J. Biol. Chem."},{"key":"2298_CR42","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1681\/ASN.2006050498","volume":"18","author":"F Peng","year":"2007","unstructured":"Peng, F. et al. RhoA activation in mesangial cells by mechanical strain depends on caveolae and caveolin-1 interaction. J. Am. Soc. Nephrol. 18, 189\u2013198 (2007).","journal-title":"J. Am. Soc. Nephrol."},{"key":"2298_CR43","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.bbrc.2013.03.097","volume":"434","author":"RD Singh","year":"2013","unstructured":"Singh, R. D. et al. Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis. Biochem Biophys. Res Commun. 434, 466\u2013472 (2013).","journal-title":"Biochem Biophys. Res Commun."},{"key":"2298_CR44","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1074\/jbc.M409040200","volume":"280","author":"A Beardsley","year":"2005","unstructured":"Beardsley, A. et al. Loss of caveolin-1 polarity impedes endothelial cell polarization and directional movement. J. Biol. Chem. 280, 3541\u20133547 (2005).","journal-title":"J. Biol. Chem."},{"key":"2298_CR45","doi-asserted-by":"publisher","first-page":"7232","DOI":"10.1074\/jbc.M607396200","volume":"282","author":"XH Sun","year":"2007","unstructured":"Sun, X. H. et al. Identification of a novel domain at the N terminus of caveolin-1 that controls rear polarization of the protein and caveolae formation. J. Biol. Chem. 282, 7232\u20137241 (2007).","journal-title":"J. Biol. Chem."},{"key":"2298_CR46","doi-asserted-by":"publisher","first-page":"40659","DOI":"10.1074\/jbc.M407051200","volume":"279","author":"E Gonzalez","year":"2004","unstructured":"Gonzalez, E. et al. Small interfering RNA-mediated down-regulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J. Biol. Chem. 279, 40659\u201340669 (2004).","journal-title":"J. Biol. Chem."},{"key":"2298_CR47","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1096\/fj.04-2682fje","volume":"19","author":"A Brouet","year":"2005","unstructured":"Brouet, A. et al. Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide. FASEB J. 19, 602\u2013604 (2005).","journal-title":"FASEB J."},{"key":"2298_CR48","doi-asserted-by":"publisher","first-page":"7675","DOI":"10.1158\/0008-5472.CAN-06-4697","volume":"67","author":"L Cantiani","year":"2007","unstructured":"Cantiani, L. et al. Caveolin-1 reduces osteosarcoma metastases by inhibiting c-Src activity and met signaling. Cancer Res. 67, 7675\u20137685 (2007).","journal-title":"Cancer Res."},{"key":"2298_CR49","doi-asserted-by":"publisher","first-page":"C993","DOI":"10.1152\/ajpcell.00023.2016","volume":"310","author":"C Zhang","year":"2016","unstructured":"Zhang, C. et al. Caveolin-1 regulates corneal wound healing by modulating Kir4.1 activity. Am. J. Physiol. Cell Physiol. 310, C993\u2013C1000 (2016).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2298_CR50","doi-asserted-by":"publisher","first-page":"527","DOI":"10.2119\/molmed.2010.00046","volume":"16","author":"JH Rhim","year":"2010","unstructured":"Rhim, J. H. et al. Caveolin-1 as a novel indicator of wound-healing capacity in aged human corneal epithelium. Mol. Med 16, 527\u2013534 (2010).","journal-title":"Mol. Med"},{"key":"2298_CR51","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.ydbio.2018.11.015","volume":"445","author":"R Yang","year":"2019","unstructured":"Yang, R. et al. Role of caveolin-1 in epidermal stem cells during burn wound healing in rats. Dev. Biol. 445, 271\u2013279 (2019).","journal-title":"Dev. Biol."},{"key":"2298_CR52","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.jid.2017.12.001","volume":"138","author":"S Elliot","year":"2018","unstructured":"Elliot, S. et al. A modeling conundrum: murine models for cutaneous wound healing. J. Invest Dermatol 138, 736\u2013740 (2018).","journal-title":"J. Invest Dermatol"},{"key":"2298_CR53","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1016\/j.celrep.2018.10.024","volume":"25","author":"R Moreno-Vicente","year":"2018","unstructured":"Moreno-Vicente, R. et al. Caveolin-1 modulates mechanotransduction responses to substrate stiffness through actin-dependent control of YAP. Cell Rep. 25, 1622\u20131635 (2018). e6.","journal-title":"Cell Rep."},{"key":"2298_CR54","doi-asserted-by":"publisher","first-page":"H936","DOI":"10.1152\/ajpheart.00519.2004","volume":"288","author":"C Radel","year":"2005","unstructured":"Radel, C. & Rizzo, V. Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization. Am. J. Physiol. Heart Circ. Physiol. 288, H936\u2013H945 (2005).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2298_CR55","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nrm2122","volume":"8","author":"RG Parton","year":"2007","unstructured":"Parton, R. G. & Simons, K. The multiple faces of caveolae. Nat. Rev. Mol. Cell Biol. 8, 185\u2013194 (2007).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2298_CR56","doi-asserted-by":"publisher","first-page":"L775","DOI":"10.1152\/ajplung.00327.2009","volume":"298","author":"Y Wang","year":"2010","unstructured":"Wang, Y. et al. A role for caveolin-1 in mechanotransduction of fetal type II epithelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. 298, L775\u2013L783 (2010).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"2298_CR57","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14932-6","volume":"7","author":"YC Yeh","year":"2017","unstructured":"Yeh, Y. C. et al. Mechanotransduction of matrix stiffness in regulation of focal adhesion size and number: reciprocal regulation of caveolin-1 and beta1 integrin. Sci. Rep. 7, 15008 (2017).","journal-title":"Sci. Rep."},{"key":"2298_CR58","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1083\/jcb.201003086","volume":"191","author":"A Hayer","year":"2010","unstructured":"Hayer, A. et al. Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradation. J. Cell Biol. 191, 615\u2013629 (2010).","journal-title":"J. Cell Biol."},{"key":"2298_CR59","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1083\/jcb.200506103","volume":"170","author":"A Tagawa","year":"2005","unstructured":"Tagawa, A. et al. Assembly and trafficking of caveolar domains in the cell: caveolae as stable, cargo-triggered, vesicular transporters. J. Cell Biol. 170, 769\u2013779 (2005).","journal-title":"J. Cell Biol."},{"key":"2298_CR60","doi-asserted-by":"crossref","unstructured":"Pol, A. et al. Non-caveolar caveolins - duties outside the caves. J. Cell Sci. 133, jcs241562 (2020).","DOI":"10.1242\/jcs.241562"},{"key":"2298_CR61","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1091\/mbc.e17-05-0278","volume":"28","author":"F Meng","year":"2017","unstructured":"Meng, F. et al. The phospho-caveolin-1 scaffolding domain dampens force fluctuations in focal adhesions and promotes cancer cell migration. Mol. Biol. Cell 28, 2190\u20132201 (2017).","journal-title":"Mol. Biol. Cell"},{"key":"2298_CR62","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1016\/S0002-9440(10)63920-X","volume":"162","author":"G Cao","year":"2003","unstructured":"Cao, G. et al. Disruption of the caveolin-1 gene impairs renal calcium reabsorption and leads to hypercalciuria and urolithiasis. Am. J. Pathol. 162, 1241\u20131248 (2003).","journal-title":"Am. J. Pathol."},{"key":"2298_CR63","doi-asserted-by":"publisher","first-page":"6494","DOI":"10.1074\/jbc.M115.687004","volume":"291","author":"S Sethna","year":"2016","unstructured":"Sethna, S. et al. Regulation of phagolysosomal digestion by caveolin-1 of the retinal pigment epithelium is essential for vision. J. Biol. Chem. 291, 6494\u20136506 (2016).","journal-title":"J. Biol. Chem."},{"key":"2298_CR64","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1111\/iwj.12327","volume":"13","author":"N Ojeh","year":"2016","unstructured":"Ojeh, N. et al. The effects of caffeine on wound healing. Int Wound J. 13, 605\u2013613 (2016).","journal-title":"Int Wound J."},{"key":"2298_CR65","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/978-1-62703-505-7_14","volume":"1037","author":"O Stojadinovic","year":"2013","unstructured":"Stojadinovic, O. & Tomic-Canic, M. Human ex vivo wound healing model. Methods Mol. Biol. 1037, 255\u2013264 (2013).","journal-title":"Methods Mol. Biol."},{"key":"2298_CR66","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1073\/pnas.0407224102","volume":"102","author":"PN Bernatchez","year":"2005","unstructured":"Bernatchez, P. N. et al. Dissecting the molecular control of endothelial NO synthase by caveolin-1 using cell-permeable peptides. Proc. Natl Acad. Sci. USA 102, 761\u2013766 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2298_CR67","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1038\/82176","volume":"6","author":"M Bucci","year":"2000","unstructured":"Bucci, M. et al. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat. Med. 6, 1362\u20131367 (2000).","journal-title":"Nat. Med."},{"key":"2298_CR68","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1007\/s10571-011-9694-1","volume":"31","author":"M Schmitz","year":"2011","unstructured":"Schmitz, M., Zerr, I. & Althaus, H. H. Effect of cavtratin, a caveolin-1 scaffolding domain peptide, on oligodendroglial signaling cascades. Cell Mol. Neurobiol. 31, 991\u2013997 (2011).","journal-title":"Cell Mol. Neurobiol."},{"key":"2298_CR69","doi-asserted-by":"publisher","first-page":"e80946","DOI":"10.1371\/journal.pone.0080946","volume":"8","author":"H Qin","year":"2013","unstructured":"Qin, H. & Bollag, W. B. The caveolin-1 scaffolding domain peptide decreases phosphatidylglycerol levels and inhibits calcium-induced differentiation in mouse keratinocytes. PLoS One 8, e80946 (2013).","journal-title":"PLoS One"},{"key":"2298_CR70","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.abb.2012.05.023","volume":"525","author":"I Jozic","year":"2012","unstructured":"Jozic, I., Saliba, S. C. & Barbieri, M. A. Effect of EGF-receptor tyrosine kinase inhibitor on Rab5 function during endocytosis. Arch. Biochem. Biophys. 525, 16\u201324 (2012).","journal-title":"Arch. Biochem. Biophys."},{"key":"2298_CR71","first-page":"20","volume":"1","author":"I Jozic","year":"2011","unstructured":"Jozic, I., Blanco, G. & Barbieri, M. A. Inhibition of Rab5 activation during insulin receptor-mediated endocytosis. Curr. Cell Biochem 1, 20\u201332 (2011).","journal-title":"Curr. Cell Biochem"},{"key":"2298_CR72","doi-asserted-by":"publisher","unstructured":"Carlson, M. W., Alt-Holland, A., Egles, C. & Garlick, J. A. Three-dimensional tissue models of normal and diseased skin. Curr. Protoc. Cell Biol. https:\/\/doi.org\/10.1002\/0471143030.cb1909s41 (2008). Chapter 19: Unit 19.9.","DOI":"10.1002\/0471143030.cb1909s41"},{"key":"2298_CR73","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.1242\/jcs.00474","volume":"116","author":"N Maas-Szabowski","year":"2003","unstructured":"Maas-Szabowski, N., Starker, A. & Fusenig, N. E. Epidermal tissue regeneration and stromal interaction in HaCaT cells is initiated by TGF-alpha. J. Cell Sci. 116, 2937\u20132948 (2003).","journal-title":"J. Cell Sci."},{"key":"2298_CR74","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1046\/j.1523-1747.1999.00573.x","volume":"112","author":"HJ Stark","year":"1999","unstructured":"Stark, H. J. et al. Organotypic keratinocyte cocultures in defined medium with regular epidermal morphogenesis and differentiation. J. Invest Dermatol 112, 681\u2013691 (1999).","journal-title":"J. Invest Dermatol"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02298-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02298-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02298-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T14:26:29Z","timestamp":1670077589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02298-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,18]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2298"],"URL":"https:\/\/doi.org\/10.1038\/s42003-021-02298-5","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,18]]},"assertion":[{"value":"11 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"757"}}