کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10801736 | 1055632 | 2016 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Unfolded protein response induced by Brefeldin A increases collagen type I levels in hepatic stellate cells through an IRE1α, p38 MAPK and Smad-dependent pathway
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کلمات کلیدی
Jnkinositol-requiring enzyme 1 alphaPBABFAATF6αERKHSCIRE1α - IRE1aMAPK - MAPKp38 MAPK - P38 MAPKPKR-like ER kinase - PK-like ER kinasePhenylbutyric acid - اسید فینیل بوتیریکbrefeldin A - برفلدین AHepatic stellate cells - سلولهای ستارهای کبدیendoplasmic reticulum - شبکه آندوپلاسمی activating transcription factor 6α - فعال کردن عامل رونویسی 6αUnfolded protein response - پاسخ پروتئین آشکارmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenp38 mitogen-activated protein kinase - پروتئین کیناز متیوژن فعال p38PERK - پرکCollagen type I - کلاژن نوع Iextracellular-regulated kinase - کیناز تنظیم شده خارج سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Unfolded protein response (UPR) triggered as a consequence of ER stress has been shown to be involved in the development of different pathologies, including fibrotic disorders. In the present paper we explore the role played by UPR on a key fibrogenic parameter in the liver: collagen type I levels in activated hepatic stellate cells (HSC). Using Brefeldin A (BFA) as an ER stress inducer we found that UPR correlated with enhanced mRNA and protein levels of collagen type I in a cell line of immortalized non-tumoral rat HSC. Analysis of the three branches of UPR revealed the activation of IRE1α, PERK and ATF6 in response to BFA, although PERK activation was shown not to be involved in the fibrogenic action of BFA. BFA also activated p38 MAPK in an IRE1α-dependent way and the p38 MAPK inhibitor SB203580 prevented the increase in collagen type I mRNA and protein levels caused by BFA, suggesting the involvement of this kinase on this effect. Analysis of Smad activation showed that phosphorylated nuclear levels of Smad2 and 3 were increased in response to BFA treatment. Inhibition of Smad3 phosphorylation by SIS3 prevented the enhancement of collagen type I levels caused by BFA. Pretreatment with IRE1α and p38 MAPK inhibitors also prevented the increased p-Smad3 accumulation in the nucleus, suggesting an IRE1α-p38 MAPK-Smad pathway to be responsible for the fibrogenic action of BFA on HSC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 8, August 2016, Pages 2115-2123
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 8, August 2016, Pages 2115-2123
نویسندگان
Marina Ruiz de Galarreta, Amaia Navarro, Eduardo Ansorena, Antonia GarcÃa Garzón, Teresa Mòdol, MarÃa J. López-Zabalza, Juan J. MartÃnez-Irujo, MarÃa J. Iraburu,