Journal
EXPERIMENTAL DERMATOLOGY
Volume 24, Issue 9, Pages 698-702Publisher
WILEY-BLACKWELL
DOI: 10.1111/exd.12752
Keywords
bleomycin; lysophosphatidic acid receptor; mouse model; scleroderma
Categories
Ask authors/readers for more resources
The study of lysophosphatidic acid (LPA) receptor has recently focused on its involvement in the pathogenesis of systemic sclerosis (SSc). We examined the inhibitory effects of the antagonist for the LPA receptor, a selective LPA(1) and LPA(3) antagonist (Ki16425), on dermal and lung fibrosis in a mouse model of SSc. Ki16425 was administered intra-dermally after 6h on the same sites as bleomycin injection. Histopathological examination showed that skin lesions were markedly attenuated by treatment with Ki16425 at doses of 1 and 10mg/kg, along with reduced dermal thickness. Hydroxyproline contents in the Ki16425-treated skin showed a decrease of 35% (1mg/kg) and 45% (10mg/kg) compared with those in the oil-injected skin of the controls. The number of mast cells and phospho-Smad2/3-positive spindle cells of the Ki16425-treated skin was significantly decreased compared with that in the controls. Additionally, RT-PCR analysis showed that the mRNA levels of TGF-1, CTGF, MIP-1, IFN- and collagen 1(I) were significantly decreased in both the 1-mg/kg and 10-mg/kg groups of the Ki16425-treated mice compared with those in the controls. Furthermore, treatment with bleomycin and Ki16425 showed reduction in lung fibrosis, and the hydroxyproline contents in the lungs of the Ki16425-treated mice showed a decrease of 25% (1mg/kg) and 32% (10mg/kg) compared with those in the lungs of the controls. Taken together, Ki16425 was found to improve dermal and lung fibrosis in a mouse model of bleomycin-induced murine scleroderma. These results suggest that Ki16425 has the potential to be an effective new treatment for scleroderma.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available