TRPV1 Involvement in Inflammatory Tissue Fibrosis in Mice
TRPV1 Involvement in Inflammatory Tissue Fibrosis in Mice
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DOI：
10.1016/j.ajpath.2011.02.043
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发表时间：
2011-06-01
影响因子：
6
通讯作者：
Saika, Shizuya
中科院分区：
文献类型：
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作者：
Okada, Yuka;Reinach, Peter S.;Saika, Shizuya
我们使用小鼠角膜碱烧伤模型，研究了瞬时受体电位香草酸亚型 1 (TRPV1) 的缺失或阻断是否会影响受伤组织愈合过程中的炎症和纤维化/疤痕水平。将 1 N NaOH 滴注到 TRPV1 -/- (KO) (n = 88) 或 TRPV1+1+ (n = 94) 小鼠的一只眼睛中，产生角膜烧伤。对角膜表面和眼球大小的检查表明，TRPV1 的缺失抑制了碱烧伤后的炎症和纤维化/疤痕形成，组织学、IHC 和基因表达分析证实了这一点。 TRPV1 的缺失抑制炎症细胞侵袭和肌成纤维细胞生成，并与促炎和促纤维化成分表达减少相关。任一基因型小鼠之间的骨髓移植实验表明，KO 角膜组织驻留细胞（而不是 KO 骨髓衍生细胞）负责 KO 型伤口愈合，并减少炎症和纤维化。 TRPV1的缺失减弱了培养的眼成纤维细胞中转化生长因子β1（TGFβ1）的表达和其他促炎基因的表达，但不影响巨噬细胞中TGFβ1的表达。 TRPV1 的缺失会抑制培养的成纤维细胞中肌成纤维细胞的转分化。全身性 TRPV1 拮抗剂再现了 KO 类型的愈合。总之，TRPV1 缺失或阻断碱烧伤小鼠角膜的愈合。 TRPV1 是改善炎症/纤维化伤口愈合结果的潜在药物靶点。 （Am J Pathol 2011，178：2654-2664；DOI：10.1016/j.ajpath.2011.02.043）
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+1+ (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 beta 1 (TGF beta 1) and other proinflammatory gene expression in cultured ocular fibroblasts, but did not affect TGF beta 1 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 healing of alkali-burned mouse cornea. TRPV1 is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing. (Am J Pathol 2011, 178:2654-2664; DOI: 10.1016/j.ajpath.2011.02.043)