Essential role of microfibrillar-associated protein 4 in human cutaneous homeostasis and in its photoprotection

Sci Rep. 2011;1:164. doi: 10.1038/srep00164. Epub 2011 Nov 22.

Abstract

UVB-induced cutaneous photodamage/photoaging is characterized by qualitative and quantitative deterioration in dermal extracellular matrix (ECM) components such as collagen and elastic fibers. Disappearance of microfibrillar-associated protein 4 (MFAP-4), a possible limiting factor for cutaneous elasticity, was documented in photoaged dermis, but its function is poorly understood. To characterize its possible contribution to photoprotection, MFAP-4 expression was either augmented or inhibited in a human skin xenograft photodamage murine model and human fibroblasts. Xenografted skin with enhanced MFAP-4 expression was protected from UVB-induced photodamage/photoaging accompanied by the prevention of ECM degradation and aggravated elasticity. Additionally, remarkably increased or decreased fibrillin-1-based microfibril development was observed when fibroblasts were treated with recombinant MFAP-4 or with MFAP-4-specific siRNA, respectively. Immunoprecipitation analysis confirmed direct interaction between MFAP-4 and fibrillin-1. Taken together, our findings reveal the essential role of MFAP-4 in photoprotection and offer new therapeutic opportunities to prevent skin-associated pathologies.

MeSH terms

  • Animals
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology
  • Elasticity
  • Extracellular Matrix Proteins / antagonists & inhibitors
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Extracellular Matrix Proteins / pharmacology
  • Fibrillin-1
  • Fibrillins
  • Glycoproteins / antagonists & inhibitors
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Glycoproteins / pharmacology
  • Homeostasis
  • Humans
  • Mice
  • Microfilament Proteins / metabolism
  • RNA, Small Interfering / genetics
  • Recombinant Proteins / pharmacology
  • Skin / drug effects
  • Skin / metabolism*
  • Skin / radiation effects
  • Skin Aging / physiology
  • Skin Physiological Phenomena
  • Transplantation, Heterologous
  • Ultraviolet Rays / adverse effects

Substances

  • Carrier Proteins
  • Extracellular Matrix Proteins
  • FBN1 protein, human
  • Fbn1 protein, mouse
  • Fibrillin-1
  • Fibrillins
  • Glycoproteins
  • MFAP4 protein, human
  • Microfilament Proteins
  • RNA, Small Interfering
  • Recombinant Proteins