Skin　fibrosis　is　characterized　by　excessive　proliferation　of　fibroblasts　and　overproduction　of　extracellular　matrix　(ECM).　C1/qtumor　necrosis　factor-related　protein　6　(CTRP6),　a　member　of　CTRPs,　has　been　involved　in　the　development　of　cardiac　fibrosis.　However,　the　function　and　detailed　regulatory　mechanism　of　CTRP6　in　skin　fibrosis　remain　unclear.　The　aim　of　this　study　was　to　investigate　the　effect　of　CTRP6　on　the　activation　of　human　dermal　fibroblasts.　Our　results　showed　that　CTRP6　was　lowly　expressed　in　scar　tissues　and　transforming　growth　factor-beta　1　(TGF-beta　1)-treated　dermal　fibroblasts.　CTRP6　over　expression　significantly　inhibited　the　proliferation　of　dermal　fibroblasts,　as　well　as　suppressed　the　expression　of　ECM　in　TGF-beta　1-treated　dermal　fibroblasts.　Furthermore,　CTRP6　overexpression　markedly　inhibited　TGF-beta　1-induced　phosphorylation　of　Smad3　in　dermal　fibroblasts.　In　conclusion,　the　data　reported　here　demonstrate　that　CTRP6　is　able　to　inhibit　the　proliferation　and　ECM　expression　in　human　dermal　fibroblasts　through　suppressing　the　TGF-beta　1/Smad3　signaling　pathway.　These　findings　suggest　that　CTRP6　may　be　a　potential　therapeutic　target　for　the　prevention　of　skin　fibrosis.　(C)　2016　Elsevier　Inc.　All　rights　reserved.