The endogenous protease inhibitor TIMP-1 mediates protection and recovery from Cutaneous Photodamage

Urara Yokose, Akira Hachiya, Penkanok Sriwiriyanont, Tsutomu Fujimura, Marty O. Visscher, William J. Kitzmiller, Alexander Bello, Ryoji Tsuboi, Takashi Kitahara, Gary P. Kobinger, Yoshinori Takema

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

UVB exposure is well known to induce skin photodamage and photoaging that correlates with qualitative and quantitative deterioration of the dermal extracellular matrix (ECM) because of the upregulation of matrix metalloproteinases (MMPs). Although inhibitory effects of tissue inhibitor of metalloproteinases (TIMPs) on most MMPs have been reported, the protective role of TIMP-1 against photodamage is poorly understood. To address this, TIMP-1 function was augmented or abolished in a human skin xenograft photodamage model after the confirmation of significantly diminished TIMP-1 expression both in photoaged and intrinsically aged skins. During a chronic UVB exposure regimen, pre-treatment with a lentiviral vector overexpressing TIMP-1 or concomitant administration of an anti-TIMP-1-neutralizing antibody (NAB) led to photoprotection or more severe photodamage, respectively. Overexpression of TIMP-1 resulted in significant inhibition of UVB-induced ECM degradation, as well as suppression of decreased skin elasticity and roughness, whereas the NABmediated inhibition of TIMP-1 had opposite effects. Furthermore, UVB-induced production of the proinflammatory cytokine, tumor necrosis factor a, was inhibited by TIMP-1 treatment of human keratinocytes. Taken together, these data shed light on the important role of TIMP-1 in protection and recovery from cutaneous photodamage because of its suppression of ECM degradation and inflammation.

Original languageEnglish (US)
Pages (from-to)2800-2809
Number of pages10
JournalJournal of Investigative Dermatology
Volume132
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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