Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S]

Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. “Stimulated by re...

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Main Authors: Chao-Hung Chen, Liang-Yin Ke, Hua-Chen Chan, An-Sheng Lee, Kun-Der Lin, Chih-Sheng Chu, Mei-Yueh Lee, Pi-Jung Hsiao, Chin Hsu, Chu-Huang Chen, Shyi-Jang Shin
Format: Article
Language:English
Published: Elsevier 2016-08-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520352159
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language English
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author Chao-Hung Chen
Liang-Yin Ke
Hua-Chen Chan
An-Sheng Lee
Kun-Der Lin
Chih-Sheng Chu
Mei-Yueh Lee
Pi-Jung Hsiao
Chin Hsu
Chu-Huang Chen
Shyi-Jang Shin
spellingShingle Chao-Hung Chen
Liang-Yin Ke
Hua-Chen Chan
An-Sheng Lee
Kun-Der Lin
Chih-Sheng Chu
Mei-Yueh Lee
Pi-Jung Hsiao
Chin Hsu
Chu-Huang Chen
Shyi-Jang Shin
Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S]
Journal of Lipid Research
lectin-like oxidized LDL receptor-1
stimulated by retinoic acid 6
renal tubular cells
author_facet Chao-Hung Chen
Liang-Yin Ke
Hua-Chen Chan
An-Sheng Lee
Kun-Der Lin
Chih-Sheng Chu
Mei-Yueh Lee
Pi-Jung Hsiao
Chin Hsu
Chu-Huang Chen
Shyi-Jang Shin
author_sort Chao-Hung Chen
title Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S]
title_short Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S]
title_full Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S]
title_fullStr Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S]
title_full_unstemmed Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S]
title_sort electronegative low density lipoprotein induces renal apoptosis and fibrosis: stra6 signaling involved[s]
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2016-08-01
description Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. “Stimulated by retinoic acid 6” (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1−/− mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease.
topic lectin-like oxidized LDL receptor-1
stimulated by retinoic acid 6
renal tubular cells
url http://www.sciencedirect.com/science/article/pii/S0022227520352159
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spelling doaj-fd524eded23d4739b5e3e9519fec57e52021-04-29T04:38:07ZengElsevierJournal of Lipid Research0022-22752016-08-0157814351446Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved[S]Chao-Hung Chen0Liang-Yin Ke1Hua-Chen Chan2An-Sheng Lee3Kun-Der Lin4Chih-Sheng Chu5Mei-Yueh Lee6Pi-Jung Hsiao7Chin Hsu8Chu-Huang Chen9Shyi-Jang Shin10Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Health Sciences, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Lipid Science and Aging Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Lipid Science and Aging Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Medicine,Mackay Medical College, New Taipei, TaiwanDivisions of Endocrinology and Metabolism Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanCardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDivisions of Endocrinology and Metabolism Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDivisions of Endocrinology and Metabolism Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Departments of Internal Medicine College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanPhysiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanTo whom correspondence should be addressed. (C-H.C.); (S-J.S.); Lipid Science and Aging Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Vascular and Medical Research,Texas Heart Institute, Houston, TX; To whom correspondence should be addressed. (C-H.C.); (S-J.S.)To whom correspondence should be addressed. (C-H.C.); (S-J.S.); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Lipid Science and Aging Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Divisions of Endocrinology and Metabolism Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Departments of Internal Medicine College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; To whom correspondence should be addressed. (C-H.C.); (S-J.S.)Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. “Stimulated by retinoic acid 6” (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFβ1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1−/− mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease.http://www.sciencedirect.com/science/article/pii/S0022227520352159lectin-like oxidized LDL receptor-1stimulated by retinoic acid 6renal tubular cells