TRPV1 Involvement in Inflammatory Tissue Fibrosis in Mice

Abstract

We examined whether absence or blocking of transient receptor potential vanilloid subtype 1 (TRPV1) affects the level of inflammation and fibrosis/scarring during healing of injured tissue using an alkali burn model of cornea in mice. A cornea burn was produced with 1 N NaOH instilled into one eye of TRPV1-/- (KO) (n = 88) or TRPV1+/+ (n = 94) mice. Examinations of the corneal surface and eye globe size suggested that the loss of TRPV1 suppressed inflammation and fibrosis/scarring after alkali burn, and this was confirmed by histology, IHC, and gene expression analysis. The loss of TRPV1 inhibited inflammatory cell invasion and myofibroblast generation in association with reduction of expression of proinflammatory and profibrogenic components. Experiments of bone marrow transplantation between either genotype of mice showed that KO corneal tissue resident cells, but not KO bone marrow-derived cells, are responsible for KO-type wound healing with reduced inflammation and fibrosis. The absence of TRPV1 attenuated expression of transforming growth factor β 1 (TGFβ1) and other proinflammatory gene expression in cultured ocular fibroblasts, but did not affect TGFβ1 expression in macrophages. Loss of TRPV1 inhibited myofibroblast transdifferentiation in cultured fibroblasts. Systemic TRPV1 antagonists reproduced the KO type of healing. In conclusion, absence or blocking of TRPV1 suppressed inflammation and fibrosis/scarring during healing of alkali-burned mouse cornea. TRPV1 is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing.

Upregulation of Transient Receptor Potential Vanilloid Type-1 Channel Activity and Ca2+Influx Dysfunction in Human Pterygial Cells

“…Cellular constituent release caused by a severe chemical injury also induces TRPV1 activation, followed by corneal opacification and chronic dysregulated inflammation during wound healing. 27,28,31,32 As increases in cell proliferation in cancer are associated with rises in functional TRPV1 expression and activity, 33,34 we hypothesized that this change is associated with conjunctival hyperplasia in pterygium.…”

Is dry eye an environmental disease?

“…Members of the transient receptor potential (TRP) channel superfamily, which include subfamilies in corneal epithelial and keratocytes, respond to environmental irritants inducing afferent impulses to the central nervous system (79) . Chemical burns in mice induce a specific TRP vanilloid type 1 (TRPV1) channel deregulated inflammatory responses leading to corneal melt and opacification (80) . The injury-induced inflammatory and opacification responses resulting from TRPV1 activation were attributed to the up regulation of pro inflammatory and chemo attractive cytokines.…”

Role of vitamin A in the healing process of alkali caused corneal injury of adult male albino rat: Histological and immunohistochemical study

“…In accordance, Okada et al [17] added that the involvement of inflammatory cells and disorganization of collagen fibers in the wound healing process of an alkali-burned cornea leads to further release of fibrogenic cytokines that augment the tissue inflammation and subsequent corneal scarring. Also this was in agreement with Torricelli et al [16] who stated that highly disorganized extracellular matrix was observed in corneas with haze.…”