Inhibition of MMPs Cat G and downregulates the signaling of TGF-β/Smad in chronic photodamaged human fibroblasts

Y. Zheng, Q.-F. Xu, H.-Y. Chen, C.-X. Ye, W. Lai, H.I. Maibach

Department of Dermato-venereology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China. drlaiwei@163.com

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• Dermatology

OBJECTIVE: To understand the action of Cathepsin G (Cat G) and matrix metalloproteases (MMPs) on the β/Smad pathway of transforming growth factor β (TGF-β) in chronically photodamaged human fibroblasts. Cat G plays a significant role in the process of skin photoaging and in collagen synthesis and degradation which is induced by UV irradiation it could interact with TGF-β/Smad signaling. No available studies have thoroughly explored its molecular mechanisms of photoaging regulation.

PATIENTS AND METHODS: Fibroblasts were divided into 4 groups: (1) control, (2) UVA irradiation of 25 J/cm2, (3) UVA irradiation of 25 J/cm2 + MMPs inhibitor, and (4) 25 J/cm2 UVA irradiation + Cat G inhibitor. All treatments were repeated daily for 21 days. Western blot and ELISA was employed to detect Protein levels for Cat G, MMPs, and several smads.

RESULTS: Compared to UVA-irradiated cells, the addition of MMPs inhibitor downregulated the expression of smad2, smad3, and smad4 as well as TGF-β. The addition of Cat G inhibitor downregulated the expression of smad2, smad3, and smad4 as well as TGF-β. These data suggest that TGF-β/Smad signaling was decreased by inhibition of MMPs and Cat G decreased in chronically human fibroblasts which are photo-damaged.

CONCLUSIONS: These results may help expand our knowledge of mechanisms mediating photoaging and is possibly instrumental to the exploration of novel anti-photoaging treatments.

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