Proteoglycan expression during transforming growth factor β-induced keratocyte-myofibroblast transdifferentiation
Proteoglycan expression during transforming growth factor β-induced keratocyte-myofibroblast transdifferentiation
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DOI：
10.1074/jbc.m107596200
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发表时间：
2001-11-23
影响因子：
4.8
通讯作者：
Roth, MR
中科院分区：
文献类型：
--
作者：
Funderburgh, JL;Funderburgh, ML;Roth, MR
角膜基质的角膜细胞分泌被认为是角膜透明度所必需的蛋白聚糖分子的独特群体。在愈合的角膜伤口中，角膜细胞响应于转化生长因子β（TGF-β）表现出成肌纤维细胞表型，其特征在于α-平滑肌肌动蛋白的表达。本研究检测了TGF-β诱导的角膜基质细胞-肌成纤维细胞转化过程中角膜基质细胞蛋白多糖和胶原蛋白的表达。TGF-β处理的原代牛角膜细胞产生成肌纤维细胞特征，包括锚定到含桩蛋白的粘着斑的肌动蛋白应力纤维、细胞相关纤连蛋白、α 1整合素和α-平滑肌肌动蛋白。I型和III型胶原蛋白和mRNA的增加是对TGF-β的反应。[S-35]硫酸盐标记的硫酸角质素蛋白多糖的分泌在对TGF-β的反应中显著减少。然而，硫酸皮肤素蛋白聚糖的大小和丰度增加。正常基质蛋白聚糖（lumican、keratocan、mimecan和核心蛋白聚糖）的蛋白质和mRNA转录物均在对TGF-β的反应中降低，但双糖蛋白聚糖（纤维化组织中存在的蛋白聚糖）的蛋白质表达和mRNA显著上调。这些结果表明，TGF-β在体外诱导的蛋白多糖表达模式类似于体内角膜瘢痕的蛋白多糖表达模式。这种改变的蛋白聚糖表达与转分化协调发生。角膜细胞的肌纤维母细胞表型，暗示这些细胞的来源，纤维组织在不透明的角膜疤痕。
Keratocytes of the corneal stroma secrete a unique population of proteoglycan molecules considered essential for corneal transparency. In healing corneal wounds, keratocytes exhibit a myofibroblastic phenotype in response to transforming growth factor beta (TGF-beta), characterized by expression of a-smooth muscle actin. This study examined proteoglycan and collagen expression by keratocytes in vitro during the TGF-beta induced keratocyte-myofibroblast transition. TGF-beta treated primary bovine keratocytes developed myofibroblastic features, including actin stress fibers anchored to paxillin-containing focal adhesions, cell-associated fibronectin, a, integrin, and a-smooth muscle actin. Collagen I and III protein and mRNA increased in response to TGF-beta. Secretion of [S-35]sulfate-labeled keratan sulfate proteoglycans decreased markedly in response to TGF-beta. Dermatan sulfate proteoglycans, however, increased in size and abundance. Protein and mRNA transcripts for normal stromal proteoglycans (lumican, keratocan, mimecan, and decorin) all decreased in response to TGF-beta, but protein expression and mRNA for biglycan, a proteoglycan present in fibrotic tissue, was markedly up-regulated. These results show that TGF-beta in vitro induces a proteoglycan expression pattern similar to that of corneal scars in vivo. This altered proteoglycan expression occurred coordinately with transdifferentiation. of keratocytes to the myofibroblastic phenotype, implicating these cells as the source of fibrotic tissue in nontransparent corneal scars.