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

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Correia Sa, I (Author) Other; Carvalho, C (Author) Other; Machado, VA (Author) Other; Carvalho, S (Author) Other; Maria Paula Serrão (Author) FMUP; Marisa Marques (Author) FMUP; vieira-coelho, ma (Author) FMUP

Journal

Title: Fundamental and Clinical Pharmacology

ISSN: 0767-3981

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00V-AAK

DOI: 10.1111/fcp.12716

Abstract (EN): 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-beta (10 ng/ml). Fibroblast activation into myofibroblasts was quantified by the expression of alpha-smooth muscle actin (alpha-SMA) using Immunocytochemistry and Western Blot assays. Collagen content was quantified with the Sirius red staining assay. Upon human fibroblasts stimulation with TGF-beta, a significant increase on alpha-SMA and CB2 receptor expression was observed. In these cells, JWH133 decreased alpha-SMA expression and collagen content. However, this effect was not observed in resting human fibroblasts. AM630 decreased alpha-SMA expression and collagen content in both resting and activated fibroblasts. This effect was time- and concentration-dependent with an IC50 value of 11 mu M. The CB2 receptor appears to be involved in fibroblast repair during skin wound healing in humans, as TGF-beta 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11