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- Title
Age-related reduction of dermal fibroblast size upregulates multiple matrix metalloproteinases as observed in aged human skin in vivo.
- Authors
Qin, Z.; Balimunkwe, R.M.; Quan, T.
- Abstract
Background Fragmentation of collagen fibrils, the major structure protein in skin, is a hallmark of dermal ageing. Matrix metalloproteinases ( MMPs) are largely responsible for the fragmentation of collagen fibrils. Objectives To quantify gene expression of all 23 known mammalian MMPs in sun-protected young and aged human skin in vivo and to investigate the potential mechanism underlying age-related alteration of multiple MMPs. Methods MMP mRNA expression levels and MMP activity in sun-protected young and aged human skin in vivo were determined by real-time reverse transcription polymerase chain reaction ( RT- PCR) and in situ zymography, respectively. The relative contributions to elevated MMPs in epidermis and dermis were quantified by laser capture microdissection coupled real-time RT- PCR. Dermal fibroblast morphology and collagen fibril fragmentation in human skin in vivo were assessed by second-harmonic generation microscopy and atomic force microscopy, respectively. In vitro cell morphology was assessed by CellTracker® fluorescent dye (Molecular Probes, Eugene, OR, U.S.A.) and phalloidin staining. Protein levels were determined by ProteinSimple capillary electrophoresis immunoassay (ProteinSimple, Santa Clare, CA, U.S.A.). Results Multiple MMPs are elevated in aged human skin dermis. Increased MMP activity and collagen fibril fragmentation were observed in aged skin dermis. As dermal fibroblasts are the major MMP-producing cells in the dermis, reduction of dermal fibroblast size, which is observed in aged human skin, contributes to the elevation of age-related multiple MMPs. Reduction of fibroblast size upregulates c-Jun/c-Fos and activates AP-1. Conclusions Combined actions of the wide variety of MMPs that are constitutively elevated in aged dermis may be involved in the progressive degradation of dermal collagen fibrils. Age-related elevations of multiple MMPs are likely to be a result of the reduction of fibroblast size via activation of AP-1.
- Subjects
FIBROBLASTS; METALLOPROTEINASE genetics; METALLOPROTEINASE regulation; HUMAN skin color genetics; AGE factors in human body composition
- Publication
British Journal of Dermatology, 2017, Vol 177, Issue 5, p1337
- ISSN
0007-0963
- Publication type
Article
- DOI
10.1111/bjd.15379