Substance P and fibrotic diseases

Substance P (SP) is an undecapeptide encoding the tachykinin 1 (TAC1) gene and belongs to the tachykinin family. SP is widely distributed in the central nervous system and the peripheral nervous system. SP is also produced by nonneuronal cells, such as inflammatory cells and endothelial cells. The biological activities of SP are mainly regulated through the high-affinity neurokinin 1 receptor (NK-1R). The SP/NK-1R system plays an important role in the molecular bases of many human pathophysiologic processes, such as pain, infectious and inflammatory diseases, and cancer. In addition, this system has been implicated in fibrotic diseases and processes such as wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, and lung fibrosis. Recently, studies have shown that SP plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of fibrosis. NK-1R receptor antagonists could provide clinical solutions for fibrotic diseases. This review summarizes the structure and function of SP and its involvement in fibrotic diseases.