Transient Receptor Potential Channels and Corneal Stromal Inflammation.
Transient Receptor Potential Channels and Corneal Stromal Inflammation.
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瞬时受体电位通道和角膜基质炎症。
DOI：
10.1097/ico.0000000000000602
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发表时间：
2015
期刊：
影响因子：
2.8
通讯作者：
Saika S
中科院分区：
文献类型：
--
作者：
0kada Y,Reinach PS,Shirai K,Kitano-Izutani A,Miyajima M,Yamanaka O,Sumioka T;Saika S
角膜透明度取决于其上皮和内皮限制层以及基质的结构完整性和功能活性的维持。不同的瞬时受体电位（TRP）通道亚型在细胞和角膜感觉神经末梢上表达。它们作为环境刺激的传感器和换能器，可以降低组织透明度。这些非选择性阳离子通道是共享TRP盒蛋白序列同源性的超家族的成员，该超家族具有6个跨膜结构域，在第五和第六区段之间具有孔。TRP通道由4个单体亚基组成，这些亚基以同源或异源构型寡聚化，这些构型源自属于相同或6个不同亚家族中的任一个的不同TRP亚型。在角膜中鉴定的TRP亚家族成员包括属于典型、香草素、锚蛋白或melastatin亚家族的那些。在这篇综述中，我们特别关注TRPV1和TRPA1在角膜中表达的功能作用，因为它们的激活提供了对有害环境应激的适应性伤害性和免疫反应，例如刺激性配体、温度波动、环境渗透压升高、机械拉伸、pH下降和组织损伤。我们以前的研究表明，TRPV1和TRPA1亚型是改善碱烧伤后角膜伤口愈合的潜在药物靶点，因为TRPV1或TRPA1基因沉默小鼠中损伤诱导的纤维化，新血管形成和炎症都显着减少。
Corneal transparency is dependent on the maintenance of the structural integrity and functional activity of its epithelial and endothelial limiting layers and the stroma. Different transient receptor potential (TRP) channel subtypes are expressed in cells and on corneal sensory nerve endings. They serve as sensors and transducers of environmental stimuli that can reduce tissue transparency. These nonselective cation channels are members of a superfamily sharing TRP box protein sequence homology having 6 membrane spanning domains with a pore between the fifth and sixth segments. TRP channels are composed of 4 monomeric subunits that oligomerize in homomeric or heteromeric configurations derived from different TRP subtypes belonging to the same or any of 6 different subfamilies. TRP subfamily members identified in the cornea include those belonging to the canonical, vanilloid, ankyrin, or melastatin subfamilies. In this review, we specifically focus on the functional roles of TRPV1 and TRPA1 expression in the cornea as their activation provides adaptive nociceptive and immune responses to noxious environmental stresses such as irritating ligands, temperature fluctuations, rises in ambient osmolarity, mechanical stretch, decline in pH, and tissue injury. Our previous studies have indicated that TRPV1 and TRPA1 subtypes are potential drug targets for improving corneal wound healing after alkali burns, because injury-induced fibrosis, neovascularization, and inflammation in either TRPV1 or TRPA1 gene-silenced mice were all significantly reduced.