Exogenous supply of Hsp47 triggers fibrillar collagen deposition in skin cell cultures in vitro

dc.bibliographicCitation.firstPage22eng
dc.bibliographicCitation.issue1eng
dc.bibliographicCitation.journalTitleBMC Molecular and Cell Biologyeng
dc.bibliographicCitation.lastPage196eng
dc.bibliographicCitation.volume21eng
dc.contributor.authorKhan, E.S.
dc.contributor.authorSankaran, S.
dc.contributor.authorLlontop, L.
dc.contributor.authorDel Campo, A.
dc.date.accessioned2020-07-24T06:49:30Z
dc.date.available2020-07-24T06:49:30Z
dc.date.issued2020
dc.description.abstractBackground: Collagen is a structural protein that provides mechanical stability and defined architectures to skin. In collagen-based skin disorders this stability is lost, either due to mutations in collagens or in the chaperones involved in collagen assembly. This leads to chronic wounds, skin fragility, and blistering. Existing approaches to treat such conditions rely on administration of small molecules to simulate collagen production, like 4-phenylbutyrate (4-PBA) or growth factors like TGF-β. However, these molecules are not specific for collagen synthesis, and result in unsolicited side effects. Hsp47 is a collagen-specific chaperone with a major role in collagen biosynthesis. Expression levels of Hsp47 correlate with collagen deposition. This article explores the stimulation of collagen deposition by exogenously supplied Hsp47 (collagen specific chaperone) to skin cells, including specific collagen subtypes quantification. Results: Here we quantify the collagen deposition level and the types of deposited collagens after Hsp47 stimulation in different in vitro cultures of cells from human skin tissue (fibroblasts NHDF, keratinocytes HaCat and endothelial cells HDMEC) and mouse fibroblasts (L929 and MEF). We find upregulated deposition of fibrillar collagen subtypes I, III and V after Hsp47 delivery. Network collagen IV deposition was enhanced in HaCat and HDMECs, while fibril-associated collagen XII was not affected by the increased intracellular Hsp47 levels. The deposition levels of fibrillar collagen were cell-dependent i.e. Hsp47-stimulated fibroblasts deposited significantly higher amount of fibrillar collagen than Hsp47-stimulated HaCat and HDMECs. Conclusions: A 3-fold enhancement of collagen deposition was observed in fibroblasts upon repeated dosage of Hsp47 within the first 6 days of culture. Our results provide fundamental understanding towards the idea of using Hsp47 as therapeutic protein to treat collagen disorders.eng
dc.description.versionpublishedVersioneng
dc.identifier.urihttps://doi.org/10.34657/3712
dc.identifier.urihttps://oa.tib.eu/renate/handle/123456789/5083
dc.language.isoengeng
dc.publisherLondon : BioMed Centraleng
dc.relation.doihttps://doi.org/10.1186/s12860-020-00267-0
dc.relation.issn2661-8850
dc.rights.licenseCC BY 4.0 Unportedeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/eng
dc.subject.ddc570eng
dc.subject.otherCollagen depositioneng
dc.subject.otherCollagen fibrilseng
dc.subject.otherExtracellular matrixeng
dc.subject.otherHsp47eng
dc.subject.othercollagen type 1eng
dc.subject.othercollagen type 12eng
dc.subject.othercollagen type 3eng
dc.subject.othercollagen type 4eng
dc.subject.othercollagen type 5eng
dc.subject.otherfibril associated collageneng
dc.subject.otherfibrillar collageneng
dc.subject.otherheat shock protein 47eng
dc.subject.otheranimal celleng
dc.subject.otherArticleeng
dc.subject.othercell cultureeng
dc.subject.othercell densityeng
dc.subject.othercell differentiationeng
dc.subject.othercell surfaceeng
dc.subject.othercollagen fibrileng
dc.subject.othercollagen synthesiseng
dc.subject.othercontrolled studyeng
dc.subject.otherendocytosiseng
dc.subject.otherendothelium celleng
dc.subject.otherextracellular matrixeng
dc.subject.otherHaCat cell lineeng
dc.subject.otherhumaneng
dc.subject.otherhuman celleng
dc.subject.otherkeratinocyteeng
dc.subject.otherMEF cell lineeng
dc.subject.othermouseeng
dc.subject.othermyofibroblasteng
dc.subject.otherNCTC clone 929 cell lineeng
dc.subject.othernonhumaneng
dc.subject.otherskin celleng
dc.subject.otherskin fibroblasteng
dc.titleExogenous supply of Hsp47 triggers fibrillar collagen deposition in skin cell cultures in vitroeng
dc.typeArticleeng
dc.typeTexteng
tib.accessRightsopenAccesseng
wgl.contributorINMeng
wgl.subjectBiowissenschaften/Biologieeng
wgl.typeZeitschriftenartikeleng
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