ReferenceID 4474

Alpinetin Suppresses Effects of TGF-β1 on Stimulating the Production and Organization of Fibrotic Markers in Human Primary Dermal Fibroblasts

Cells

Overgrowths of dermal fibroblasts and myofibroblast phenoconversion in response to TGF-β stimulation are the hallmarks of skin fibrosis. Constitutive activation of dermal fibroblasts by TGF-β induces the excessive produc

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Reference Id
4474
Evidence Id
21064
Core Evidence Id
21064
Source Reference Id
2232
Herb2 Reference Id
HBREF003029
Subject Paper Key
HBIN015751_36078140
Pubmed Id
36078140
Doi
10.3390/cells11172731
Paper Title
Alpinetin Suppresses Effects of TGF-β1 on Stimulating the Production and Organization of Fibrotic Markers in Human Primary Dermal Fibroblasts
Paper Abstract
Overgrowths of dermal fibroblasts and myofibroblast phenoconversion in response to TGF-β stimulation are the hallmarks of skin fibrosis. Constitutive activation of dermal fibroblasts by TGF-β induces the excessive production of extracellular matrix as well as certain key intracellular proteins which form a complex interaction network. Current therapies include monoclonal anti-bodies against TGF-β and surgery, but these treatments generally elicit a limited effect on certain kinds of skin fibrosis. In the current study, we investigated the effects of alpinetin (AP) on human primary dermal fibroblasts (HPDFs) stimulated with TGF-β1. Results demonstrated that AP exhibited strong inhibitory effects on TGF-β1-induced proliferation and migration of HPDFs. AP also inhibited TGF-β1-induced morphological changes of fibroblasts to myofibroblasts, and these were found to be from its effects on blocking actin stress fiber formation and organization. The expression of major fibrotic molecules including α-SMA and type I collagen upon TGF-β1 stimulation was also inhibited by AP. In addition, AP attenuated TGF-β1-induced production and organization of vimentin, β-catenin, and N-cadherin, important for the pathophysiology of skin fibrosis. In conclusion, we revealed that AP has an ability to reverse the fibrotic effects of TGF-β1 at the cellular level, and this discovery suggests the therapeutic potential of AP for skin fibrosis.
Journal
Cells
Publish Year
2022
Experiment Subject
human
Experiment Type
Cell Experiment
Phenotype Related
Skin Fibrosis
Paper Title Cn
Paper Title En
Alpinetin Suppresses Effects of TGF-β1 on Stimulating the Production and Organization of Fibrotic Markers in Human Primary Dermal Fibroblasts
Bilingual Status
semi_complete