TNBS誘発大腸繊維化におけるマクロファージTRPM2の役割

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  • Role of TRPM2 expressed in macrophages in TNBS-induced colonic fibrosis in mice

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<p>Background: TRPM2 is known to be expressed in intestinal immune cells including macrophages and involved in the progression of colitis. Since pathological fibrosis in the intestinal tract impairs quality of life and requires surgery, it is a clinical major problem. In this study, we investigated the role of TRPM2 in intestinal fibrosis using TNBS-induced mouse fibrosis models.</p><p>Materials &amp; Methods: Male TRPM2-deficient mice (KO) and wild-type mice (WT) were used. The colonic fibrosis was evaluated by measuring the length of colon, fibrosis score under Masson's-trichrome staining, mRNA expression of COL1A1, ACTA2, TIMP1 and TRPM2 by quantitative RT-PCR.</p><p>Results: Repeated colorectal injection of TNBS induced shortening of colon length, increasing fibrosis score, and upregulating COL1A1,ACTA2,TIMP1 mRNA expressions in WT mice, but these responses were significantly attenuated in KO mice. TRPM2 expression was significantly upregulated in mucosa and muscular layer of the colon, and in bone marrow induced by TNBS treatment. In addition, TNBS-induced colonic fibrosis was significantly suppressed in WT mice transplanted with bone marrow cells from KO compared with mice transplanted with bone marrow from WT. TRPM2 deficiency significantly attenuated LPS-induced increase in TNF-α, IL-6, and IL-1β expressions in macrophages differentiated from bone marrow cells. </p><p>Conclusion: TRPM2 expressed in bone marrow cell-derived macrophages contributes to the pathogenesis of in TNBS-induced colonic fibrosis.</p>

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