Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice.

Critical in vivo roles of WNT10A in wound healing by regulating collagen expression/synthesis in WNT10A-deficient mice.
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DOI:
10.1371/journal.pone.0195156
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Kohno K
Kohno K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang KY;Yamada S;Izumi H;Tsukamoto M;Nakashima T;Tasaki T;Guo X;Uramoto H;Sasaguri Y;Kohno K

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我们已经报道,WNT10A在成纤维细胞/肌成纤维细胞和微血管内皮细胞的生长中起关键作用,即伤口愈合/瘢痕形成。为了确定WNT10A在体内的调节和中枢功能,我们使用WNT10A缺陷小鼠(WNT10A-/-)检测了WNT10A缺失的净效应。我们建立了WNT10A-/-小鼠,表现出一系列独特的形态/器官发生失败的表型,如生长迟缓、脱发、后凸和不孕,然后重点研究WNT10A在伤口愈合中的作用。我们用C57BL/6J野生型(WT)或WNT10A-/-小鼠进行皮肤溃疡形成。与WNT10A-/-小鼠相比,WNT10A-/-小鼠的损伤面积明显更大,伤口愈合延迟,这与(A)成纤维细胞/肌成纤维细胞和微血管数量较少,以及(B)胶原表达和合成更少有关,尤其是在那些具有激活的肌成纤维细胞的WT小鼠。这些观察表明,WNT10A信号在体内可以通过调节胶原的表达和合成在伤口愈合中发挥关键作用,作为促纤维化因子之一,至少在一定程度上,WNT10A介导的伤口有效愈合的体内关键作用与胶原的表达密切相关。
We have reported that WNT10A plays a critical role in the growth of fibroblasts/myofibroblasts and microvascular endothelial cells, i.e.; wound healing/scarring. To ascertain the in vivo regulatory, central functions of WNT10A, we examined the net effects of WNT10A depletion using WNT10A-deficient mice (WNT10A–/–). We generated WNT10A–/–mice, displaying a range of unique phenotypes of morpho/organogenetic failure, such as growth retardation, alopecia, kyphosis and infertility, and then focused on the functions of WNT10A in wound healing. We subjected C57BL/6J wild-type (WT) or WNT10A–/–mice to skin ulcer formation. The WNT10A–/–mice had significantly larger injured areas and delayed wound healing, which were associated with (a) a smaller number of fibroblasts/myofibroblasts and microvessels; and (b) more reduced expression and synthesis of collagen, compared with WT mice with intact WNT10A expression, especially in those with activated myofibroblasts. These observations indicate that WNT10A signaling can play a pivotal in vivo role in wound healing by regulating the expression and synthesis of collagen, as one of fibrogenic factors, at least in part, and critical in vivo roles of WNT10A-mediated effective wound healing are extremely closely associated with collagen expression.
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