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Transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) is an important pro\u2010fibrotic modulator of ECM metabolism, whose levels are elevated in human POAG lamina cribrosa tissue compared with non\u2010glaucomatous controls. We hypothesize that in POAG, lamina cribrosa (LC) glial cells respond to elevated TGF\u2010\u03b2, producing a remodeled ONH ECM. Using Affymetrix microarrays, we report the first study examining the effect of TGF\u2010\u03b21 on global gene expression profiles in glial fibrillary acidic acid (GFAP)\u2010negative LC glial cells in vitro. Prominent among the differentially expressed genes were those with established fibrogenic potential, including CTGF, collagen I, elastin, thrombospondin, decorin, biglycan, and fibromodulin. Independent TaqMan and Sybr Green quantitative PCR analysis significantly validated genes involved in regulation of cell proliferation (platelet\u2010derived growth factor [PDGF\u2010\u03b1]), angiogenesis (vascular endothelial growth factor [VEGF]), ECM accumulation and degradation (CTGF, IL\u201011, and ADAMT\u2010S5), and growth factor binding (ESM\u20101). Bioinformatic analysis of the ESM\u20101 promoter identified putative Smad and Runx transcription factor binding sites, and luciferase assays confirmed that TGF\u2010\u03b21 drives transcription of the ESM\u20101 gene. TGF\u2010\u03b21 induces expression and release of ECM components in LC cells, which may be important in regulating matrix remodeling in the lamina cribrosa. In disease states such as POAG, the LC cell may represent an important pro\u2010fibrotic cell type and an attractive target for novel therapeutic strategies. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20247","type":"journal-article","created":{"date-parts":[[2005,8,3]],"date-time":"2005-08-03T21:56:59Z","timestamp":1123106219000},"page":"309-324","source":"Crossref","is-referenced-by-count":86,"title":["Transforming growth factor\u2010\u03b2\u2010regulated gene transcription and protein expression in human GFAP\u2010negative lamina cribrosa cells"],"prefix":"10.1002","volume":"52","author":[{"given":"Ruaidhr\u00ed P.","family":"Kirwan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin O.","family":"Leonard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbot F.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colm J.","family":"O'Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,8,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.8.1913"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1969.00990020792015"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-004-1092-7"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000025758"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.6.3099"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0484fje"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.01-1282"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/19.2.185"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(91)32345-5"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00010.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.4.9912011"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100008200"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0649"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-5155(01)00414-2"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(99)00017-8"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1997.01100150391013"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(87)90165-6"},{"key":"e_1_2_6_19_1","first-page":"78","article-title":"Cell culture of the human lamina cribrosa","volume":"29","author":"Hernandez MR","year":"1988","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(14)75984-7"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1136(200011)32:2<122::AID-GLIA20>3.0.CO;2-J"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10051"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00306.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.5.1345"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.56.4.3"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-10-r70"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.4.6.637"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng015"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00441-4"},{"key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"12684","DOI":"10.1016\/S0021-9258(18)99930-8","article-title":"Functional analysis of human alpha 1(I) procollagen gene promoter. 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