کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5703982 1602558 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TNF-α upregulates HIF-1α expression in pterygium fibroblasts and enhances their susceptibility to VEGF independent of hypoxia
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی و میکروب شناسی (عمومی)
پیش نمایش صفحه اول مقاله
TNF-α upregulates HIF-1α expression in pterygium fibroblasts and enhances their susceptibility to VEGF independent of hypoxia
چکیده انگلیسی
The clinical manifestations of pterygium are characterized by rapid growth and postoperative recurrences. We had previously proposed that hypoxia-inducible factor (HIF)-1α recruits progenitor cells during the development and progression of pterygia. Recently, it was reported that various stimuli, including inflammation, could activate HIF-1α even under normoxic conditions. The ocular surface directly faces external environments, and is thus frequently exposed to inflammatory insults. First, we examined the gene expression of HIF-1α, its downstream molecule, vascular endothelial growth factor (VEGF)-A, and VEGF receptor (VEGFR)-2 in corneal and conjunctival cells compared with cultured human umbilical vein endothelial cells. Corneal fibroblasts had high expression of VEGFR-2 in the presence of TNF-α, and HIF-1α was activated by TNF-α in diverse ocular surface cells. The HIF-1α/VEGF/VEGFR signaling pathway in response to TNF-α was evaluated in cultured human pterygium fibroblasts (HPFs) at the gene and protein levels and was compared to treatment with cobalt chloride (CoCl2), a hypoxic mimetic, to exclude the effect of hypoxia. Although VEGF-A expression was not changed by TNF-α, expression of HIF-1α and VEGFR-2 was enhanced in HPFs treated with TNF-α, independent of hypoxia conditioning. In addition, VEGF-C gene expression was activated solely by TNF-α in HPF, but VEGF-B levels were not significantly affected. These results may provide mechanistic explanations for the uniquely vigorous proliferation of pterygium fibrovascular tissue during TNF-α-induced ocular surface inflammation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 164, November 2017, Pages 74-81
نویسندگان
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