TIPARP is involved in the regulation of intraocular pressure.
TIPARP is involved in the regulation of intraocular pressure.
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TIPARP 参与眼压调节
DOI：
10.1038/s42003-022-04346-0
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发表时间：
2022-12-19
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
眼内压（IOP）升高是青光眼的主要危险因素。IOP升高的分子机制尚不清楚，这阻碍了青光眼的治疗。2,3,7,8 - 四氯二苯并 - 对 - 二恶英（TCDD）诱导型聚ADP - 核糖聚合酶（TIPARP）是PARP家族的一员，可催化单ADP - 核糖基化。在此我们表明，TIPARP在人眼的角膜、小梁网、虹膜、视网膜、视神经、巩膜和脉络膜中广泛表达。与健康对照组相比，原发性开角型青光眼患者的血液和小梁网中TIPARP的表达显著上调。转录组分析显示，在TIPARP上调的人小梁网（HTM）细胞中，与细胞外基质沉积和细胞黏附相关的基因表达降低。此外，蛋白质印迹分析表明，在TIPARP下调或TIPARP受抑制的HTM细胞中，I型和IV型胶原蛋白、纤连蛋白和α - 平滑肌肌动蛋白增加。此外，这些细胞中产生了交联的肌动蛋白网络，纽蛋白上调。对Sprague - Dawley大鼠进行TIPARP抑制剂RBN - 2397结膜下注射会使IOP升高。因此，我们确定TIPARP通过调节HTM细胞中的细胞外基质和细胞骨架蛋白来调节IOP。这些结果表明，TIPARP是高眼压和青光眼的一个潜在治疗靶点。
TIPARP是一种诱导型聚ADP - 核糖聚合酶，被确定为通过调节小梁网细胞中的细胞外基质和细胞骨架蛋白来调节眼内压的一种新型调节因子。
Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. The molecular mechanism of elevated IOP is unclear, which impedes glaucoma therapy. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible Poly-ADP-ribose Polymerase (TIPARP), a member of the PARP family, catalyses mono-ADP-ribosylation. Here we showed that TIPARP was widely expressed in the cornea, trabecular meshwork, iris, retina, optic nerve, sclera, and choroid of human eyes. The expression of TIPARP was significantly upregulated in the blood and trabecular meshwork of patients with primary open angle glaucoma compared with that of healthy controls. Transcriptome analysis revealed that the expression of genes related to extracellular matrix deposition and cell adhesion was decreased inTIPARP-upregulated human trabecular meshwork (HTM) cells. Moreover, western blot analysis showed that collagen types I and IV, fibronectin, and α-SMA were increased inTIPARP-downregulated or TIPARP-inhibited HTM cells. In addition, cross-linked actin networks were produced, and vinculin was upregulated in these cells. Subconjunctival injection of the TIPARP inhibitor RBN-2397 increased the IOP inSprague–Dawleyrats. Therefore, we identified TIPARP as a regulator of IOP through modulation of extracellular matrix and cell cytoskeleton proteins in HTM cells. These results indicate that TIPARP is a potential therapeutic target for ocular hypertension and glaucoma.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.4
作者：
Filla MS;Schwinn MK;Sheibani N;Kaufman PL;Peters DM
通讯作者：
Peters DM
影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
影响因子：
14.9
作者：
MacPherson L;Tamblyn L;Rajendra S;Bralha F;McPherson JP;Matthews J
通讯作者：
Matthews J
影响因子：
4.4
作者：
Kirwan, Ruaidhri P.;Felice, Luca;Leonard, Martin O.
通讯作者：
Leonard, Martin O.