Hevin plays a pivotal role in corneal wound healing.
Hevin plays a pivotal role in corneal wound healing.
复制标题
DOI：
10.1371/journal.pone.0081544
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mehta JS
中科院分区：
文献类型：
--
作者：
Chaurasia SS;Perera PR;Poh R;Lim RR;Wong TT;Mehta JS
Hevin是一种通过与周围细胞外基质（ECM）蛋白相互作用参与组织修复和重塑的基质细胞蛋白。在这项研究中，我们研究了hevin的功能作用，使用角膜基质伤口愈合模型，通过准分子激光诱导的不规则光治疗性角膜切除术（IrrPTK）在hevin空（hevin-/-）小鼠。我们还研究了外源性补充重组人hevin（rhHevin）对受准分子激光损伤的基质细胞成分的拯救作用。将野生型（WT）和hevin -/-小鼠在4个时间点（1、2、3和4周）分成三组。第一组为未接受任何治疗的患者。Ⅱ组行上皮清创术，用准分子激光行IrrPTK。第三组在IrrPTK术后局部应用rhHevin 3天。使用裂隙灯生物显微镜、体内共聚焦显微镜、光学显微镜（LM）、透射电子显微镜（TEM）、免疫组织化学（IHC）和蛋白质印迹（WB）分析眼睛的角膜混浊和基质重塑组分。IHC显示IrrPTK损伤的WT小鼠中hevin的上调。与WT组相比，Hevin -/-小鼠早在IrrPTK治疗后1-2周就出现角膜混浊，其在3-4周达到峰值。它们还表现出炎性细胞、ECM蛋白的纤维化组分和血管化角膜的积累，如通过IHC和WB所见。光镜和透射电镜显示基质中有活化的角膜细胞（肌成纤维细胞）、炎性碎片和血管组织。外源性应用rhHevin 3天恢复了与WT小鼠相似的角膜基质炎症指数。 Hevin在IrrPTK损伤的角膜中瞬时表达，并且Hevin的损失使它们倾向于异常伤口愈合。Hevin -/-小鼠发生早期角膜混浊，其特征在于严重的慢性炎症和基质纤维化，可以通过外源性施用rhHevin来挽救。因此，hevin在角膜创伤愈合中起着关键作用。
Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin-/-) mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin) to rescue the stromal cellular components damaged by the excimer laser. Wild type (WT) and hevin -/- mice were divided into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM), transmission electron microscopy (TEM), immunohistochemistry (IHC) and western blotting (WB). IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin -/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts), inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin -/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued with exogenous administration of rhHevin. Thus, hevin plays a pivotal role in the corneal wound healing.
登录
查看更多内容
影响因子：
3.4
作者：
Mohan, Rajiv R.;Stapleton, W. Michael;Wilson, Steven E.
通讯作者：
Wilson, Steven E.
影响因子：
13.7
作者：
Gambato, C;Ghirlando, A;Midena, E
通讯作者：
Midena, E
影响因子：
4.8
作者：
Hambrock, HO;Nitsche, DP;Hartmann, U
通讯作者：
Hartmann, U
影响因子：
6
作者：
Hisatomi, Toshio;Nakao, Shintaro;Miller, Joan W.
通讯作者：
Miller, Joan W.
DOI：
10.1007/s004170000182
发表时间：
2000-10-01
影响因子：
2.7
作者：
Li, Q;Ashraf, MF;O'Brien, TP
通讯作者：
O'Brien, TP