دورية أكاديمية
أعرض في EDS

Role of PAI-1 in hepatic steatosis and dyslipidemia.

التفاصيل البيبلوغرافية
العنوان: Role of PAI-1 in hepatic steatosis and dyslipidemia.
المؤلفون: Levine JA; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA., Oleaga C; Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA., Eren M; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA., Amaral AP; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA., Shang M; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA., Lux E; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA., Khan SS; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA., Shah SJ; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA., Omura Y; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA., Pamir N; Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA., Hay J; Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA., Barish G; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.; Department of Medicine, Jesse Brown VA Medical Center, Chicago, IL, USA., Miyata T; Department of Molecular Medicine and Therapy, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan., Tavori H; Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA., Fazio S; Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA., Vaughan DE; Department of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA. d-vaughan@northwestern.edu.
المصدر: Scientific reports [Sci Rep] 2021 Jan 11; Vol. 11 (1), pp. 430. Date of Electronic Publication: 2021 Jan 11.
نوع المنشور: Journal Article; Observational Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Dyslipidemias/*genetics , Fatty Liver/*genetics , Plasminogen Activator Inhibitor 1/*physiology, Animals ; Cells, Cultured ; Cohort Studies ; Dyslipidemias/metabolism ; Fatty Liver/metabolism ; Female ; Fibroblast Growth Factors/genetics ; Hep G2 Cells ; Humans ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Proprotein Convertase 9/genetics
مستخلص: Plasminogen activator inhibitor 1 (PAI-1) is a functional biomarker of the metabolic syndrome. Previous studies have demonstrated that PAI-1 is a mechanistic contributor to several elements of the syndrome, including obesity, hypertension and insulin resistance. Here we show that PAI-1 is also a critical regulator of hepatic lipid metabolism. RNA sequencing revealed that PAI-1 directly regulates the transcriptional expression of numerous genes involved in mammalian lipid homeostasis, including PCSK9 and FGF21. Pharmacologic or genetic reductions in plasma PAI-1 activity ameliorates hyperlipidemia in vivo. These experimental findings are complemented with the observation that genetic deficiency of PAI-1 is associated with reduced plasma PCSK9 levels in humans. Taken together, our findings identify PAI-1 as a novel contributor to mammalian lipid metabolism and provides a fundamental mechanistic insight into the pathogenesis of one of the most pervasive medical problems worldwide.
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معلومات مُعتمدة: R01 HL051387 United States HL NHLBI NIH HHS; R01 HL132985 United States HL NHLBI NIH HHS; T32 HL134633 United States HL NHLBI NIH HHS
المشرفين على المادة: 0 (FGF21 protein, human)
0 (Plasminogen Activator Inhibitor 1)
0 (SERPINE1 protein, human)
62031-54-3 (Fibroblast Growth Factors)
EC 3.4.21.- (PCSK9 protein, human)
EC 3.4.21.- (Proprotein Convertase 9)
تواريخ الأحداث: Date Created: 20210112 Date Completed: 20210907 Latest Revision: 20211117
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7801442
DOI: 10.1038/s41598-020-79948-x
PMID: 33432099
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-020-79948-x