Please use this identifier to cite or link to this item: doi:10.22028/D291-31047
Title: Exogenous supply of Hsp47 triggers fibrillar collagen deposition in skin cell cultures in vitro
Author(s): Khan, Essak S
Sankaran, Shrikrishnan
Llontop, Lorena
del Campo Bécares, Aránzazu
Language: English
Title: BMC Molecular and Cell Biology
Volume: 21
Publisher/Platform: BMC
Year of Publication: 2020
Free key words: Hsp47
Collagen deposition
Extracellular matrix
Collagen fibrils
DDC notations: 540 Chemistry
Publikation type: Journal Article
Abstract: Background: 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.
DOI of the first publication: 10.1186/s12860-020-00267-0
Link to this record: urn:nbn:de:bsz:291--ds-310479
ISSN: 2661-8850
Date of registration: 28-May-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Chemie
Professorship: NT - Prof. Dr. Aránzazu del Campo
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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