1. Essential role of microfibrillar-associated protein 4 in human cutaneous homeostasis and in its photoprotection.
- Author
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Kasamatsu S, Hachiya A, Fujimura T, Sriwiriyanont P, Haketa K, Visscher MO, Kitzmiller WJ, Bello A, Kitahara T, Kobinger GP, and Takema Y
- Subjects
- Animals, Carrier Proteins antagonists & inhibitors, Carrier Proteins genetics, Carrier Proteins pharmacology, Elasticity, Extracellular Matrix Proteins antagonists & inhibitors, Extracellular Matrix Proteins genetics, Extracellular Matrix Proteins pharmacology, Fibrillin-1, Fibrillins, Glycoproteins antagonists & inhibitors, Glycoproteins genetics, Glycoproteins pharmacology, Homeostasis, Humans, Mice, Microfilament Proteins metabolism, RNA, Small Interfering genetics, Recombinant Proteins pharmacology, Skin drug effects, Skin radiation effects, Skin Aging physiology, Skin Physiological Phenomena, Transplantation, Heterologous, Ultraviolet Rays adverse effects, Carrier Proteins metabolism, Extracellular Matrix Proteins metabolism, Glycoproteins metabolism, Skin metabolism
- 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.
- Published
- 2011
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