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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Format: | Article |
Language: | English |
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Elsevier
2016-08-01
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Series: | Journal of Lipid Research |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520352159 |
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doaj-fd524eded23d4739b5e3e9519fec57e5 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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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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 |