Substance P Promotes Fibrosis In Human Corneal Stroma
Marta Sloniecka, Patrik Danielson.
Umeň University, Umeň, Sweden.
Substance P (SP) is a neuropeptide which has been shown to be present in human corneal cells, keratocytes. Many studies suggest its role in various cellular processes important in wound healing such as proliferation or migration. We hypothesize that SP regulates expression of keratocyte markers, extracellular matrix (ECM) components and fibrotic markers that are overexpressed during fibrosis, in both primary keratocytes and myofibroblasts. Primary keratocytes, which were isolated from healthy human corneas obtained from the local cornea bank, and an in vitro corneal fibrosis model (myofibroblasts) were used throughout this study. The effect of SP on keratocyte and myofibroblast contractile abilities was assessed by cell contraction assay. Gene expression of keratocyte markers (keratocan and aldehyde dehydrogenase 3 family, member A1 [ALDH3A1]), ECM components (collagen I, collagen III, collagen V and lumican), and markers of fibrosis (α-smooth muscle actin [α-SMA] and fibronectin), was determined by qRT-PCR. Treatment of keratocytes with SP resulted in decreased expression of keratocan gene but increased ALDH3A expression. SP increased expression of fibrotic markers, α-SMA and fibronectin. Moreover, collagen I, collagen III and collagen V genes were also upregulated by SP. Expression of lumican was unaffected by SP. Furthermore, keratocytes treated with SP showed increased contractile abilities. Similar effects of SP were observed in the corneal fibrosis model. SP decreased keratocan, but increased ALDH3A1 gene expression. α-SMA, fibronectin, collagen I, collagen III and collagen V genes were upregulated. Expression of lumican was unaffected. Contractile abilities of myofibroblasts increased upon SP treatment. In conclusion, SP is able to regulate keratocyte marker genes and to increase expression of various ECM genes and fibrotic markers in both keratocytes and myofibroblasts. This suggests that SP might promote fibrosis in human cornea.
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