Trichostatin a inhibits corneal haze in vitro and in vivo.
Trichostatin a inhibits corneal haze in vitro and in vivo.
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DOI：
10.1167/iovs.08-2919
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发表时间：
2009-06
影响因子：
4.4
通讯作者：
Mohan RR
中科院分区：
文献类型：
--
作者：
Sharma A;Mehan MM;Sinha S;Cowden JW;Mohan RR
曲古抑素A是一种组蛋白脱乙酰酶抑制剂，已被证明在许多非眼组织中可以抑制转化生长因子-β诱导的纤维化形成。作者利用体外和体内模型评价了TsA对转化生长因子-β诱导的角膜纤维化的细胞毒性及其抗纤维化作用。人角膜成纤维细胞(HSFs)用于体外实验，新西兰白兔用于体内实验。用准分子激光进行准分子激光屈光性角膜切削术(PRK)，造成兔眼角膜混浊。台盼蓝拒染法和四甲基偶氮唑盐比色法检测TSA对角膜的细胞毒性。用裂隙灯生物显微镜对兔眼的混浊程度进行分级。实时定量聚合酶链式反应、免疫印迹或免疫细胞化学检测α-平滑肌肌动蛋白、纤维连接蛋白和IV型胶原基因或蛋白水平。采用TUNEL法检测细胞死亡情况。250 nM或更低的TSA浓度是无细胞毒性的，并且不改变正常的HSF形态或增殖。经转化生长因子-β-1处理后，SMA(9倍)、纤维连接蛋白(2.5倍)和IV型胶原(2倍)的基因和蛋白水平显著增加。TSA可使转化生长因子-β1诱导的SMA和FN基因表达水平降低60%~75%，蛋白质水平降低1·5~3·0倍，但对IV型胶原基因或蛋白水平无影响。-9 D PRK兔角膜局部应用TSA 2分钟，可显著减少体内角膜混浊。TSA在体外抑制转化生长因子-β-1诱导的人角膜细胞外基质的积聚和肌成纤维细胞的形成，并在体内显着减少兔角膜的混浊。(投资眼科VS科学。2009年；50：2695-2701)doi：10.1167/iovs.08-2919
Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to suppress TGF-β-induced fibrogenesis in many nonocular tissues. The authors evaluated TSA cytotoxicity and its antifibrogenic activity on TGF-β– driven fibrosis in the cornea with the use of in vitro and in vivo models. Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand White rabbits were used for in vivo studies. Haze in the rabbit cornea was produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of haze in the rabbit eye was graded with slit lamp biomicroscopy. Real-time PCR, immunoblotting, or immunocytochemistry was used to measure α-smooth muscle actin (SMA), fibronectin, and collagen type IV mRNA or protein levels. TUNEL assay was used to detect cell death. TSA concentrations of 250 nM or less were noncytotoxic and did not alter normal HSF morphology or proliferation. TGF-β1 treatment of HSF significantly increased mRNA and protein levels of SMA (9-fold), fibronectin (2.5-fold), and collagen type IV (2-fold). TSA treatment showed 60% to 75% decreases in TGF-β1-induced SMA and fibronectin mRNA levels and 1.5- to 3.0-fold decreases in protein levels but had no effect on collagen type IV mRNA or protein levels in vitro. Two-minute topical treatment of TSA on rabbit corneas subjected to -9 D PRK significantly decreased corneal haze in vivo. TSA inhibits TGF-β1-induced accumulation of extracellular matrix and myofibroblast formation in the human cornea in vitro and markedly decreases haze in rabbit cornea in vivo. (Invest Ophthalmol Vis Sci. 2009;50:2695–2701) DOI: 10.1167/iovs.08-2919
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影响因子：
3.4
作者：
Mohan, Rajiv R.;Stapleton, W. Michael;Wilson, Steven E.
通讯作者：
Wilson, Steven E.
DOI：
10.1016/j.bbamcr.2007.05.016
发表时间：
2007-10-01
影响因子：
5.1
作者：
Glenisson, Wendy;Castronovo, Vincent;Waltregny, David
通讯作者：
Waltregny, David
影响因子：
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作者：
FANTES, FE;HANNA, KD;SAVOLDELLI, M
通讯作者：
SAVOLDELLI, M
影响因子：
13.7
作者：
Gambato, C;Ghirlando, A;Midena, E
通讯作者：
Midena, E
影响因子：
3.4
作者：
Jester, JV;Huang, JY;Cavanagh, HD
通讯作者：
Cavanagh, HD