title: UV-mediated downregulation of the endocytic collagen receptor, Endo180, contributes to accumulation of extracellular collagen fragments in photoaged skin.
abstract: BACKGROUND
  Collagen is the most abundant protein in human skin and is responsible for its resilience. In particular during photoaging, collagen homeostasis is out of balance leading to a continuous loss of intact collagen and to the observed signs of aged skin such as diminished tensile strength and wrinkle development. The process of collagen turnover is very slow and the relevance of cellular uptake of damaged collagen, most likely mediated via Endo180 or integrin α2β1, still remains a matter of investigation.
  
  
  OBJECTIVE
  We investigated the role of different collagen receptors on dermal fibroblasts for collagen internalization and their impact on collagen homeostasis during photoaging.
  
  
  METHODS
  TaqMan Real-Time PCR, flow cytometry, UV irradiation, knockdown experiments and immunostaining.
  
  
  RESULTS
  We show that Endo180 and integrin α2 are regulated in photoaged skin and after acute UV stress in vivo and in vitro. Knockdown experiments revealed that Endo180 is essential for cellular uptake of collagen fragments by dermal fibroblasts, whereas integrin α2 is important for initial binding of collagen. UV irradiation decreases collagen endocytosis. This correlates with reduced Endo180 expression and pericellular accumulation of collagen fragments during photoaging.
  
  
  CONCLUSIONS
  Our findings correlate for the first time impaired collagen uptake via Endo180 with the pericellular accumulation of collagen fragments during photoaging. We assume an altered pericellular niche of fibroblasts in photoaged skin that has an impact on collagen homeostasis.
authors: Research & Development, Beiersdorf AG, Unnastr. 48, 20245 Hamburg, Germany.
authors: Stefanie
authors: S
authors: Tang
authors: Ralph
authors: R
authors: Lucius
authors: Horst
authors: H
authors: Wenck
authors: Stefan
authors: S
authors: Gallinat
authors: Julia M
authors: JM
authors: Weise
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003094:Collagen / Q000378:metabolism*; D020405:Dermis / Q000166:cytology; D015536:Down-Regulation / Q000528:radiation effects; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D015595:Skin Aging / Q000502:physiology* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D055815:Young Adult
chemical_list: C408294:Endo180; D039421:Integrin alpha2; D034741:RNA, Small Interfering; D011975:Receptors, Mitogen; D003094:Collagen