AM251型
敌手
体外
大麻素受体
化学
大麻素
转化生长因子
成纤维细胞
大麻素受体2型
细胞生物学
药理学
内分泌学
受体
内科学
生物
医学
生物化学
作者
Inês Correia-Sá,Cláudia Carvalho,Paula Serrão,Vera A. Machado,Sofia O. Carvalho,Marisa Marques,Maria Augusta Vieira-Coelho
标识
DOI:10.1016/j.ejphar.2020.173738
摘要
Abstract Previous studies showed that cannabinoid 1 receptor (CB1) is linked with skin fibrosis and scar tissue formation in mice. Therefore, the topical use of cannabinoids may have a role in the prevention or treatment of local fibrotic and wound healing diseases as hypertrophic scars or keloids. In this study, we asked whether CB1 activation or inactivation would change fibroblast differentiation into myofibroblast and collagen deposition in skin human fibroblast. Primary cultures of adult human fibroblasts were obtained from abdominal human skin. Cells were stimulated with transforming growth factor-beta (TGF-β, 10ng/ml) and treated with a CB1 selective agonist (arachidonyl-2-chloroethylamide, ACEA 1 μM) and an antagonist (AM251 1, 5 and 10 μM). Alpha-smooth muscle actin (α-SMA) was quantified using Immunocytochemistry and Western Blot. Collagen was quantified with Sirius Red staining assay. Significance was assessed by One-way ANOVA. P TGF-β significantly increases α-SMA expression. ACEA 1 μM significantly increases collagen deposition but does not change α-SMA expression. AM251 10 μM added in the absence and the presence of ACEA reduces α-SMA expression and collagen content in TGF-β treated cells. AM251 shows a concentration-dependent effect over collagen deposition with a pIC50 of 5.5 (4.6–6.4). TGF-β significantly increases CB1 receptor expression. CB1 inactivation with AM251 prevents fibroblasts differentiation and collagen deposition, induced by TGF-β in human fibroblasts. The outcome supports that CB1 is a molecular target for wound healing disorders and in vivo and pre-clinical studies should be implemented to clarify this premise.
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