Transient receptor potential vanilloid 4 promotes cutaneous wound healing by regulating keratinocytes and fibroblasts migration and collagen production in fibroblasts in a mouse model.

BACKGROUND: Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown. OBJECTIVE: To investigate the role of TRPV4 in cutaneous wound healing in a mouse model. METHODS: Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro. RESULTS: TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. In vitro, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in keratinocytes, and TGF-ß stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts. CONCLUSION: TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.

Kaempferol therapy improved MC903 induced-atopic dermatitis in a mouse by suppressing TSLP, oxidative stress, and type 2 inflammation.

BACKGROUND: Atopic dermatitis is a common skin disease caused by genetic susceptibility, environmental factors, immune response, and skin barrier dysfunction. Kaempferol is a natural flavonoid widely found in tea, vegetables, and fruits and has been reported to have excellent anti-inflammation activity. However, the therapeutic effect of kaempferol on atopic dermatitis is unclear. OBJECTIVE: This study aimed to elucidate the effect of kaempferol on skin inflammation in atopic dermatitis. METHODS: The suppressive effect of kaempferol administration on skin inflammation was examined using MC903-induced atopic dermatitis-like skin inflammation mouse model. Quantification of skin dermatitis and transepidermal water loss was performed. A histopathological study was performed to examine thymic stromal lymphopoietin expression, cornified envelope proteins such as filaggrin, loricrin, and involucrin, and the numbers of infiltrating inflammatory cells, including lymphocytes, macrophages, and mast cells in the dermatitis area. The expressions of IL-4 and IL-13 were investigated by qPCR and flow cytometry analysis using skin tissues. The expression of HO-1 was investigated by western blot and qPCR. RESULTS: Kaempferol therapy significantly suppressed MC903-induced dermatitis, TEWL, TSLP, and HO-1 expression, and infiltration of inflammatory cells. Kaempferol therapy improved the decreased expressions of filaggrin, loricrin, and involucrin in MC903-induced dermatitis skin site. The expressions of IL-4, and IL-13 were partially decreased in kaempferol-treated mice. CONCLUSION: Kaempferol might improve MC903-induced dermatitis via suppression of type 2 inflammation and improvement of barrier dysfunction by inhibition of TSLP expression and oxidative stress. Kaempferol might have the potential to be a new treatment for atopic dermatitis.