Targeting cannabinoid receptor 2 (CB2) limits collagen production-An in vitro study in a primary culture of human fibroblasts.

Inês Correia-Sá, Cláudia Carvalho, Vera A Machado, Sofia Carvalho, Paula Serrão, Marisa Marques, Maria A Vieira-Coelho

Fundamental & clinical pharmacology 2022 Feb

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Previous studies showed that cannabinoid 2 (CB2) receptor is involved in skin inflammation, fibrogenesis and re-epithelialization in mice, indicating that this receptor may be implicated in wound healing. Thus, topical use of cannabinoids may have a role in local fibrotic and wound healing diseases such as scars or keloids. We investigate the effect of the CB2 selective receptor agonist (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran (JWH133) and the CB2 selective receptor antagonist (6-Iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl)(4-methoxyphenyl)-methanone (AM630), on primary cultures of human fibroblasts. Primary cultures of adult human fibroblasts were obtained from abdominal human skin samples. Fibroblasts pretreated with JWH133 and/or AM630 were stimulated with TGF-β (10 ng/ml). Fibroblast activation into myofibroblasts was quantified by the expression of alpha-smooth muscle actin (α-SMA) using Immunocytochemistry and Western Blot assays. Collagen content was quantified with the Sirius red staining assay. Upon human fibroblasts stimulation with TGF-β, a significant increase on α-SMA and CB2 receptor expression was observed. In these cells, JWH133 decreased α-SMA expression and collagen content. However, this effect was not observed in resting human fibroblasts. AM630 decreased α-SMA expression and collagen content in both resting and activated fibroblasts. This effect was time- and concentration-dependent with an IC50 value of 11 μM. The CB2 receptor appears to be involved in fibroblast repair during skin wound healing in humans, as TGF-β increases CB2 receptor expression and JWH133 produces an anti-fibrotic effect in human fibroblasts. AM630 also showed an anti-fibrotic effect hypothesizing that other cannabinoid receptors, such as TRPV, may be involved in this response. © 2021 Société Française de Pharmacologie et de Thérapeutique.

Citation

Inês Correia-Sá, Cláudia Carvalho, Vera A Machado, Sofia Carvalho, Paula Serrão, Marisa Marques, Maria A Vieira-Coelho. Targeting cannabinoid receptor 2 (CB2) limits collagen production-An in vitro study in a primary culture of human fibroblasts. Fundamental & clinical pharmacology. 2022 Feb;36(1):89-99