title: Essential role of microfibrillar-associated protein 4 in human cutaneous homeostasis and in its photoprotection.
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.
authors.affiliation: Biological Science Laboratories, Kao Corporation, Haga, Tochigi, 321–3497, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kasamatsu
authors.forename: Akira
authors.initials: A
authors.lastname: Hachiya
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujimura
authors.forename: Penkanok
authors.initials: P
authors.lastname: Sriwiriyanont
authors.forename: Keiichi
authors.initials: K
authors.lastname: Haketa
authors.forename: Marty O
authors.initials: MO
authors.lastname: Visscher
authors.forename: William J
authors.initials: WJ
authors.lastname: Kitzmiller
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takema
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004548:Elasticity; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000071838:Fibrillin-1; D000071837:Fibrillins; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D015595:Skin Aging / Q000502:physiology; D012879:Skin Physiological Phenomena; D014183:Transplantation, Heterologous; D014466:Ultraviolet Rays / Q000009:adverse effects; D054392:Adipokines
chemical_list: D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D006023:Glycoproteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse; C400752:MFAP4 protein, human