Enhanced inflammation and accelerated wound closure following tetraphorbol ester application or full-thickness wounding in mice lacking hyaluronan synthases Has1 and Has3.

Enhanced inflammation and accelerated wound closure following tetraphorbol ester application or full-thickness wounding in mice lacking hyaluronan synthases Has1 and Has3.
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DOI:
10.1038/jid.2011.248
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发表时间:
2012-01
影响因子:
6.5
通讯作者:
Maytin, Edward V.
Maytin, Edward V.
中科院分区:
医学1区
文献类型:
--
作者:
Mack, Judith A.;Feldman, Ron J.;Itano, Naoki;Kimata, Koji;Lauer, Mark;Hascall, Vincent C.;Maytin, Edward V.

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透明质酸(HA)是一种丰富的基质分子,其在皮肤中的功能仍有待充分确定。为了探索HA在皮肤损伤反应中的作用,将缺乏两种HA合酶(Has 1和Has 3)但仍表达功能性Has 2的双敲除小鼠(缩写为Has 13 null)用于两种类型的实验:(i)应用12-O-十四酰基佛波醇-13-乙酸酯(TPA),和(ii)皮肤的全层创伤。未受伤的Has 1/3缺失小鼠表型正常。然而,TPA后,HA的积累,通常发生在野生型表皮钝化Has 1/3无效表皮。在切除伤口愈合实验中,Has 1/3缺失小鼠的伤口闭合明显快于野生型小鼠。与这种异常的伤口愈合,表皮和真皮HA显着减少和中性粒细胞从皮肤血管流出的显着增加,观察到在Has 1/3无效皮肤相对于野生型皮肤。有1/3的无效伤口显示肌成纤维细胞分化较早。总之,Has 1和Has 3的选择性缺失导致促炎环境,其有利于中性粒细胞的募集和真皮中的其他炎症相关变化。
Hyaluronan (HA) is an abundant matrix molecule whose functions in the skin remain to be fully defined. To explore the roles of HA in cutaneous injury responses, double-knockout mice (abbreviated as Has1/3 null) that lack two HA synthase enzymes (Has1 and Has3) but still express functional Has2, were used in two types of experiments: (i) application of 12-O-tetradecanoylphorbol-13-acetate (TPA), and (ii) full-thickness wounding of the skin. Uninjured Has1/3 null mice were phenotypically normal. However, after TPA, the accumulation of HA that normally occurs in wildtype epidermis was blunted in Has1/3 null epidermis. In excisional wound healing experiments, wound closure was significantly faster in Has1/3 null than in wildtype mice. Coincident with this abnormal wound healing, a marked decrease in epidermal and dermal HA and a marked increase in neutrophil efflux from cutaneous blood vessels were observed in Has1/3 null skin relative to wildtype skin. Has1/3 null wounds displayed an earlier onset of myofibroblast differentiation. In summary, selective loss of Has1 and Has3 leads to a pro-inflammatory milieu that favors recruitment of neutrophils and other inflammation-related changes in the dermis.
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