title: N-terminal 5-mer peptide analog P165 of amyloid precursor protein inhibits UVA-induced MMP-1 expression by suppressing the MAPK pathway in human dermal fibroblasts.
abstract: Exposure to ultraviolet (UV) radiation leads to a progressive increase in dermal damage through the degradation of collagen, which is mediated by matrix metalloproteinases (MMPs). UV radiation alters the intracellular signaling events that regulate the elaboration of MMPs. Our previous study showed that P165, the N-terminal 5-mer peptide analog of amyloid precursor protein, exerts a protective effect on ultraviolet A (UVA)-induced loss of collagen type I in human dermal fibroblasts (HDFs) by inhibiting the generation of intracellular reactive oxygen species and MMP-1. In this study, we focused on specific signal transduction pathways to elucidate the possible photoprotective mechanisms of P165 in controlling MMP-1 inhibition. Results from western blot analyses indicated that pretreatment with P165 dose-dependently inhibited UVA-induced phosphorylation of extracellular regulated protein kinases (ERK), c-Jun N-terminal kniase (JNK), p38 mitogen-activated protein kinases (MAPKs), and the phosphorylation of their downstream targets c-Jun and c-Fos. The photoprotective effects of P165 were further demonstrated in collagen type I secretion and cellular senescence induced by UVA irradiation. These findings suggest that P165 exerts photoprotective activity in UVA-treated HDFs by regulating MMP-1 generation. This activity may be mediated by inhibiting the MAPK signaling pathways. Thus, P165 is a potential agent for the prevention of skin photoaging.
authors.affiliation: Department of Dermatology and Venereology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology and Venereology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Xuan Wu Hospital, Capital Medical University, Key laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Central Laboratory, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Dermatology and Venereology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Zi-Lian
authors.initials: ZL
authors.lastname: Liu
authors.affiliation: Department of Dermatology and Venereology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China. Electronic address: zhuwei@xwh.ccmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Dermatology and Venereology, Capital Medical University, Beijing 100069, China. Electronic address: drlianshi@sina.com.
authors.forename: Shi
authors.initials: S
authors.lastname: Lian
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D024042:Collagen Type I / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012867:Skin / Q000166:cytology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D024042:Collagen Type I; D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; D048031:JNK Mitogen-Activated Protein Kinases; D001616:beta-Galactosidase; D020781:Matrix Metalloproteinase 1
keywords: 5 peptide analog of amyloid precursor protein (P165); 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (PubChem CID: 44629973); Acrylamide (PubChem CID: 6579); Glutamine (PubChem CID: 5961); Glutaraldehyde (PubChem CID: 3485); Human dermal fibroblasts; MAPKs; Phenylmethylsulfonyl fluoride (PubChem CID: 4784); Photoaging; Sodium fluoride (PubChem CID: 5235); Sodium orthovanadate (PubChem CID: 61671); Ultraviolet A