title: Cathepsin G inhibitor prevents ultraviolet B-induced photoaging in hairless mice via inhibition of fibronectin fragmentation.
abstract: BACKGROUND
  Cathepsin G, a serine protease that is activated by ultraviolet (UV) radiation, increases matrix metalloproteinase-1 (MMP-1) expression in fibroblasts through fibronectin (Fn) fragmentation and promotes the conversion of proMMP-1 to active MMP-1.
  
  
  OBJECTIVE
  This study investigated whether [2-[3-[[(1-benzoyl-4-piperidinyl)methylamino]carbonyl]-2-naphthalenyl]-1-(1-naphthalenyl)-2-oxoethyl]-phosphonic acid (KPA), a cathepsin G inhibitor, plays any role in extracellular matrix (ECM) damage in an in vitro 3D dermal equivalent (DE) and an in vivo ultraviolet B (UVB)-irradiated hairless mice.
  
  
  METHODS
  We examined the potential ECM-protective effects of a cathepsin G inhibitor in an in vitro 3D DE model and an in vivo UVB-irradiated hairless mouse skin model.
  
  
  RESULTS
  Among five known serine protease inhibitors, KPA showed the strongest potency and selectivity against cathepsin G. KPA inhibited the cathepsin G-mediated MMP-1 increase and alleviated the downregulation of mRNAs encoding collagen and tissue inhibitor of matrix metalloproteinase-1 in an in vitro 3D DE model. Most importantly, topical application of KPA (0.025%) to the dorsal skin of hairless mice enhanced collagen expression and attenuated UVB-induced Fn fragmentation and upregulation of MMP-2 and MMP-9 activities.
  
  
  CONCLUSIONS
  Cathepsin G inhibitors may be useful for the prevention of UVB-induced photoaging through amelioration of ECM damage and MMP upregulation.
authors: Bioscience Research Institute, AmorePacific Corporation R&D Center, 314-1 Bora-dong, Giheung-gu, Yongin, Kyeonggi-do, Korea.
authors: E D
authors: ED
authors: Son
authors: J H
authors: JH
authors: Shim
authors: H
authors: H
authors: Choi
authors: H
authors: H
authors: Kim
authors: K M
authors: KM
authors: Lim
authors: J H
authors: JH
authors: Chung
authors: S Y
authors: SY
authors: Byun
authors: T R
authors: TR
authors: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D056649:Cathepsin G / Q000037:antagonists & inhibitors*; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D023421:Models, Animal; D009281:Naphthalenes / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D015595:Skin Aging / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C576786:(2-(3-(((1-benzoyl-4-piperidinyl)methylamino)carbonyl)-2-naphthalenyl)-1-(1-naphthalenyl)-2-oxoethyl)phosphonic acid; D004791:Enzyme Inhibitors; D005353:Fibronectins; D009281:Naphthalenes; D009943:Organophosphorus Compounds; D010880:Piperidines; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D004549:Elastin; D056649:Cathepsin G; D020781:Matrix Metalloproteinase 1