Unfolded protein response regulation in keloid cells.
Unfolded protein response regulation in keloid cells.
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DOI：
10.1016/j.jss.2009.04.036
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发表时间：
2011-05-01
期刊：
影响因子：
--
通讯作者：
Yang GP
中科院分区：
文献类型：
--
作者：
Butler PD;Wang Z;Ly DP;Longaker MT;Koong AC;Yang GP
瘢痕疙瘩是病理性伤口愈合的常见形式，其特征在于细胞外基质的过度产生。未折叠蛋白反应（UPR）是对缺氧的细胞反应，缺氧是伤口微环境的组成部分，能够保护细胞免受错误折叠蛋白过度积累的影响。由于瘢痕疙瘩有细胞外基质分泌过多，我们假设，瘢痕疙瘩成纤维细胞（KFs）可能有增强激活的UPR相比，正常的成纤维细胞（NF）。将KF和NF置于缺氧室中0、24和48小时。我们还使用衣霉素来特异性上调UPR。通过PCR检测xbp-1剪接，并通过免疫印迹法检测三种UPR转导物的特异性抗体，来测定UPR活化。通过免疫荧光证实了KFs中XBP-1蛋白的核定位。与暴露于缺氧后的NF相比，KFs中XBP-1蛋白的活化增加。由UPR激活的另外两条途径PERK和ATF-6在KFs和NF之间显示出相当的激活。我们通过使用免疫荧光证实XBP-1的核定位增加来证实XBP-1的活化增强。与我们最初的假设，瘢痕疙瘩将有广泛的激活的UPR，我们在这里证明，有一个特定的上调的一个方面的UPR反应。与NF相比，这可能代表KF中的特定分子缺陷，并且还表明UPR的调节可用于伤口愈合治疗。
Keloids are a common form of pathologic wound healing characterized by excessive production of extracellular matrix. The unfolded protein response (UPR) is a cellular response to hypoxia, a component of the wound microenvironment, capable of protecting cells from the effects of over-accumulation of misfolded proteins. Since keloids have hypersecretion of extracellular matrix, we hypothesized that keloid fibroblasts (KFs) may have enhanced activation of the UPR compared to normal fibroblasts (NFs). KFs and NFs were placed in a hypoxia chamber for 0, 24, and 48 hrs. We also used tunicamycin to specifically up-regulate the UPR. UPR activation was assayed by PCR for xbp-1 splicing and by immunoblotting with specific antibodies for the three UPR transducers. Nuclear localization of XBP-1 protein in KFs was confirmed by immunofluorescence. There is increased activation of XBP-1 protein in KFs compared to NFs following exposure to hypoxia. PERK and ATF-6, two other pathways activated by the UPR, show comparable activation between KFs and NFs. We confirmed that there is enhanced activation of XBP-1 by demonstrating increased nuclear localization of XBP-1 using immunofluorescence. In contrast to our initial hypothesis that keloids would have broad activation of the UPR, we demonstrate here that there is a specific up-regulation of one facet of the UPR response. This may represent a specific molecular defect in KFs compared to NFs, and also suggests modulation of the UPR can be used in wound healing therapy.
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真核生物中的氧化蛋白折叠：机制和后果。
DOI：
10.1083/jcb.200311055
发表时间：
2004-02-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Tu BP;Weissman JS
通讯作者：
Weissman JS
影响因子：
19
作者：
Helenius, Ari;Marquardt, Thorsten;Braakman, Ineke
通讯作者：
Braakman, Ineke
影响因子：
3.6
作者：
Bayat, A;Bock, O;Ferguson, MWJ
通讯作者：
Ferguson, MWJ
影响因子：
2.9
作者：
Nirodi, CS;Devalaraja, R;Richmond, A
通讯作者：
Richmond, A
影响因子：
3
作者：
Butler, Paris D.;Ly, Daphne P.;Yang, George P.
通讯作者：
Yang, George P.