دورية أكاديمية
Bone marrow-derived cPLA2α contributes to renal fibrosis progression.
| العنوان: | Bone marrow-derived cPLA2α contributes to renal fibrosis progression. |
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| المؤلفون: | Montford JR; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO John.Montford@UCDenver.edu.; Denver Veterans Affairs Medical Center, Denver, CO., Lehman AMB; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO., Bauer CD; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO., Klawitter J; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO.; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO., Klawitter J; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO.; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO., Poczobutt JM; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO., Scobey M; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO., Weiser-Evans M; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO.; School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado Anschutz Medical Campus, Aurora, CO., Nemenoff RA; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO.; School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado Anschutz Medical Campus, Aurora, CO., Furgeson SB; Department of Medicine, Renal Division, University of Colorado Anschutz Medical Campus, Aurora, CO.; School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado Anschutz Medical Campus, Aurora, CO.; Denver Health and Hospitals, Denver, CO. |
| المصدر: | Journal of lipid research [J Lipid Res] 2018 Feb; Vol. 59 (2), pp. 380-390. Date of Electronic Publication: 2017 Dec 11. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0376606 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-7262 (Electronic) Linking ISSN: 00222275 NLM ISO Abbreviation: J Lipid Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: Memphis, Lipid Research, inc. |
| مواضيع طبية MeSH: | Bone Marrow/*metabolism , Group IV Phospholipases A2/*metabolism , Kidney Diseases/*metabolism , Ureteral Obstruction/*metabolism, Animals ; Fibrosis/metabolism ; Fibrosis/pathology ; Group IV Phospholipases A2/deficiency ; Group IV Phospholipases A2/genetics ; Kidney Diseases/pathology ; Mice ; Mice, Inbred C57BL ; Ureteral Obstruction/pathology |
| مستخلص: | The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2α and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine the role of cPLA2α in bone marrow-derived cells in a murine model of renal fibrosis, unilateral ureteral obstruction (UUO). WT C57BL/6J mice were irradiated and engrafted with donor bone marrow from either WT mice [WT-bone marrow transplant (BMT)] or mice deficient in cPLA2α (KO-BMT). After full engraftment, mice underwent UUO and kidneys were collected 3, 7, and 14 days after injury. Using picrosirius red, collagen-3, and smooth muscle α actin staining, we determined that renal fibrosis was significantly attenuated in KO-BMT animals as compared with WT-BMT animals. Lipidomic analysis of homogenized kidneys demonstrated a time-dependent upregulation of pro-inflammatory eicosanoids after UUO; KO-BMT animals had lower levels of many of these eicosanoids. KO-BMT animals also had fewer infiltrating pro-inflammatory CD45+CD11b+Ly6C hi macrophages and reduced message levels of pro-inflammatory cytokines. Our results indicate that cPLA2α and/or its downstream mediators, produced by bone marrow-derived cells, play a major role in eicosanoid production after renal injury and in renal fibrinogenesis. |
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| معلومات مُعتمدة: | F32 DK104475 United States DK NIDDK NIH HHS; K08 HL103774 United States HL NHLBI NIH HHS; P30 CA046934 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: cytosolic calcium-dependent group IVA phospholipase A2α; eicosanoids; extracellular matrix; inflammation; kidney; lipidomics; phospholipases/A2 |
| المشرفين على المادة: | EC 3.1.1.4 (Group IV Phospholipases A2) |
| تواريخ الأحداث: | Date Created: 20171213 Date Completed: 20190718 Latest Revision: 20210217 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5794431 |
| DOI: | 10.1194/jlr.M082362 |
| PMID: | 29229740 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1539-7262 |
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| DOI: | 10.1194/jlr.M082362 |