The Effect of the Matricellular Protein Tenascin-c on the Functional Activity of Fibroblasts in an Experimental in Vitro Injury Model

Abstract

Wound healing is a complex, multistep process involving sequential phases of inflammation, proliferation, and remodeling. Tenascin-C (TNC) is a matricellular protein actively involved in tissue regeneration. It is upregulated in response to tissue injury and plays an important role in the regulation of cell adhesion, migration, proliferation, and extracellular matrix protein synthesis. At the same time, during the early stages of wound healing, interleukin-1α (IL1α) exerts a significant effect as an alarmin that initiates inflammatory activation of fibroblasts. The objective of this study was to determine the optimal concentration of TNC stimulating both the migratory and synthetic activity of human dermal fibroblasts in vitro, including under conditions of preliminary inflammatory activation with IL1α. To this end, a comparative analysis of cell migration and proliferation was conducted, along with measurement of type I collagen synthesis using DF-1 human fibroblast cultures pre-incubated with IL1α (50 ng/mL) for 24 h, followed by the addition of recombinant TNC at concentrations of 0.05 μg/ml, 0.2 μg/ml, and 1 μg/mL. TNC exhibited a dose-dependent effect on fibroblasts: at a concentration of 0.2 μg/ml it stimulates cell migration and proliferation, accompanied by a statistically significant increase in type I collagen synthesis compared with the control. However, this level was lower than that observed at 1 μg/mL TNC, where a marked increase in collagen production was detected. Under conditions of IL1α pre-stimulation, the effects of TNC were amplified, particularly at concentrations of 0.2 μg/ml and 1 μg/ml, indicating the potential of TNC as a regulator of cellular activity within an inflammatory microenvironment. Higher concentrations did not further increase the effect. These findings may relevant in the context of to the development of biomaterials and therapeutic agents aimed at accelerating cutaneous wound healing by modulating cellular activity, which is especially relevant for the treatment of chronic or non-healing wounds.