Neurokinin-1 Receptor Regulation of Fibroblast Phenotype and Function

Injury to tissue induces the normal wound healing process to repair damage. This is a normal and critical response developed by the body to maintain short-term organ function, and therefore, survival. Should this process become aberrant, then fibrosis can develop. Fibrosis is the excess accumulation of extracellular matrix proteins. Unlike normal wound healing that is designed to maintain organ/tissue function, fibrosis interferes with the normal architecture of the organ and has long-term functional implications. Fibroblasts are the cells responsible for producing extracellular matrix in both wound healing and fibrosis. Substance P is the cognate ligand for the neurokinin-1 receptor, and both substance P and the neurokinin-1 receptor have been demonstrated to be involved in organ remodeling; this includes regulation of fibroblast function. In this review we will focus on substance P/neurokinin-1 receptor regulation of fibroblast function in the setting of both wound healing and fibrosis. This review describes actions of substance P and the neurokinin-1 receptor on fibroblasts from multiple organs, thus identifying central actions common to all fibroblasts studied. This review also identifies gaps in the literature and future directions needed to improve understanding of substance P and the neurokinin-1 receptor regulation of fibroblast phenotype.