The stimulatory effects of alpha1-adrenergic receptors on TGF-beta1, IGF-1 and hyaluronan production in human skin fibroblasts

Skin fibroblasts modulate tissue repair, wound healing and immunological responses. Adrenergic receptors (ARs) mediate important physiological functions, such as endocrine, metabolic and neuronal activity. In this study, the expression alpha 1A-ARs in human skin fibroblasts is examined and verified. Regulatory effects of alpha 1-agonist cirazoline on cell migration and the production of transforming growth factor beta 1 (TGF-beta 1), insulin-like growth factor 1 (IGF-1), hyaluronan (HA), fibronectin and procollagen type I carboxy-terminal peptide (PIP) by human skin fibroblasts are assessed and validated. alpha 1A-AR mRNA and protein were found in human skin fibroblasts WS1. Exposure of cirazoline doubled skin fibroblast migration and the increase in cell migration was attenuated by alpha 1-antagonist prazosin. TGF-beta 1 mRNA and production were enhanced after exposure to cirazoline and IGF-1 production was also increased after treatment with cirazoline. Exposure to cirazoline also enhanced HA and PIP production. The increases in TGF-beta 1, IGF-1, HA and PIP production were partially abolished in fibroblasts transfected with alpha 1A-AR short interfering RNAs, indicating that alpha 1A-ARs are involved in the cirazoline-induced increases in TGF-beta 1, IGF-1, HA and PIP production. Thus, alpha 1A-ARs are stably expressed and stimulate cell migration and TGF-beta 1, IGF-1, HA and PIP production in human skin fibroblasts. Moreover, TGF-beta 1, IGF-1, HA and PIP production and the cell migration of human skin fibroblasts are possibly modulated by natural catecholamines produced by the endocrine system or sympathetic innervation, which could directly or indirectly participate in cytokine secretion, fibroblast migration and matrix production of wound healing in the skin.