Tensile stimuli increase nerve growth factor in human dermal fibroblasts independent of tension-induced TGF ss production

Abstract

Human dermal fibroblasts (HDFs) regulate wound-healing processes in human skin, including the regeneration of skin sensory fibres, in response to various mechanical stimuli. Because nerve growth factor (NGF) has an essential role in sensory regeneration, we evaluated the possible association of NGF with mechanical stimulus-dependent cellular responses in HDFs. A cyclic tensile stimulus increased both NGF and transforming growth factor (TGF) beta 2 production, yet with different gene transcription and signal desensitization profiles. Neutralizing TGF beta with antibodies did not affect the tension-induced NGF upregulation, with significant inhibition of endogenous TGF beta 2 transcription. The treatment with LY294002, SP600125 or U0126 hindered the tension-induced TGF beta 2 upregulation, although the increase in NGF was regulated only by SP600125 or U0126, indicating the involvement of three signalling kinase pathways in the upregulation of TGF beta 2. However, the upregulation of NGF was shown to be independent of PI3K, demonstrating the independent regulation of tension-induced NGF and TGF beta production in HDFs.