TGFβ1 and TGFβ2 proteins in corneas with and without stromal fibrosis: Delayed regeneration of apical epithelial growth factor barrier and the epithelial basement membrane in corneas with stromal fibrosis.
TGFβ1 and TGFβ2 proteins in corneas with and without stromal fibrosis: Delayed regeneration of apical epithelial growth factor barrier and the epithelial basement membrane in corneas with stromal fibrosis.
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角膜中的TGFβ1和TGFβ2蛋白，具有和不基质纤维化：顶部上皮生长因子屏障的延迟再生以及具有基质纤维化的角膜上的上皮地下膜。
DOI：
10.1016/j.exer.2020.108325
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发表时间：
2021-01
影响因子：
3.4
通讯作者：
Wilson SE
中科院分区：
文献类型：
--
作者：
de Oliveira RC;Tye G;Sampaio LP;Shiju TM;DeDreu J;Menko AS;Santhiago MR;Wilson SE
本研究旨在探讨转化生长因子(TGF) β1和TGFβ2在伴间质纤维化和不伴间质纤维化兔角膜中的表达和定位，并进一步研究瘢痕性纤维化角膜上皮基膜（EBM）中有缺陷的perlecan掺入。共有120只母兔未手术，分别为- 4.5D PRK和- 9D PRK。在未受伤至术后8周的时间点进行免疫组化（IHC），每组每个时间点有4个角膜。对tgf - β1或tgf - β2进行多重免疫组化，并进行Image-J定量，以及角蛋白、vimentin、-平滑肌肌动蛋白（SMA）、perlecan、laminin- α 5、nidogen-1或CD11b。使用Imaris 3D分析评估肌成纤维细胞和纤维化发展的四周峰值角膜。与无纤维化的- 4.5D PRK角膜相比，高损伤- 9D PRK角膜的顶端上皮生长因子屏障和EBM屏障功能的延迟再生（包括EBM perlecan掺入缺陷）更大。有缺陷的顶端上皮生长因子屏障和EBM允许上皮细胞和撕裂TGFβ1和撕裂TGFβ2进入角膜基质，驱动前基质中由vimentin阳性的角膜成纤维细胞和可能的纤维细胞生成肌成纤维细胞。在一些角膜的基质中，vimentin阳性细胞和未知的vimentin阴性细胞，cd11b阴性细胞也产生tgf - β1和/或tgf - β2。tgf - β1和tgf - β2在- 9D组肌成纤维细胞发育前几周在前基质中表达水平较高。所有- 9D角膜（术后2 - 3周开始）和4个- 4.5D PRK角膜均出现显著的SMA +肌成纤维细胞和间质纤维化。与有纤维化的- 4.5D或- 9D PRK角膜相比，无纤维化的- 4.5D PRK角膜的顶端上皮生长因子屏障和/或EBM屏障功能倾向于早几周再生。手术后8周，sma阳性的肌成纤维细胞在大多数角膜中明显减少。顶上皮生长因子屏障和EBM屏障限制tgf - β1和tgf - β2进入角膜基质，以调节与瘢痕间质纤维化相关的角膜成纤维细胞和肌成纤维细胞的发育。在严重损伤的角膜中，这些屏障的延迟再生促进了肌成纤维细胞的发育，延长了肌成纤维细胞的活力，并引发了间质瘢痕纤维化。
The purpose of this study was to investigate the expression and localization of transforming growth factor (TGF) β1 and TGFβ2 in rabbit corneas that healed with and without stromal fibrosis, and to further study defective perlecan incorporation in the epithelial basement membrane (EBM) in corneas with scarring fibrosis. A total of 120 female rabbits had no surgery, −4.5D PRK, or −9D PRK. Immunohistochemistry (IHC) was performed at time points from unwounded to eight weeks after surgery, with four corneas at each time point in each group. Multiplex IHC was performed for TGFβ1 or TGFβ2, with Image-J quantitation, and keratocan, vimentin, alpha-smooth muscle actin (SMA), perlecan, laminin-alpha 5, nidogen-1 or CD11b. Corneas at the four-week peak for myofibroblast and fibrosis development were evaluated using Imaris 3D analysis. Delayed regeneration of both an apical epithelial growth factor barrier and EBM barrier function, including defective EBM perlecan incorporation, was greater in high injury −9D PRK corneas compared to −4.5D PRK corneas without fibrosis. Defective apical epithelial growth factor barrier and EBM allowed epithelial and tear TGFβ1 and tear TGFβ2 to enter the corneal stroma to drive myofibroblast generation in the anterior stroma from vimentin-positive corneal fibroblasts, and likely fibrocytes. Vimentin-positive cells and unidentified vimentin-negative, CD11b-negative cells also produce TGFβ1 and/or TGFβ2 in the stroma in some corneas. TGFβ1 and TGFβ2 were at higher levels in the anterior stroma in the weeks preceding myofibroblast development in the −9D group. All −9D corneas (beginning two to three weeks after surgery), and four −4.5D PRK corneas developed significant SMA + myofibroblasts and stromal fibrosis. Both the apical epithelial growth factor barrier and/or EBM barrier functions tended to regenerate weeks earlier in −4.5D PRK corneas without fibrosis, compared to −4.5D or −9D PRK corneas with fibrosis. SMA-positive myofibroblasts were markedly reduced in most corneas by eight weeks after surgery. The apical epithelial growth factor barrier and EBM barrier limit TGFβ1 and TGFβ2 entry into the corneal stroma to modulate corneal fibroblast and myofibroblast development associated with scarring stromal fibrosis. Delayed regeneration of these barriers in corneas with more severe injuries promotes myofibroblast development, prolongs myofibroblast viability and triggers stromal scarring fibrosis.
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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