| Title | The Attenuation of Diabetic Nephropathy by Annexin A1 via Regulation of Lipid Metabolism Through the AMPK/PPAR alpha/CPT1b Pathway |
| Authors | Wu, Liang Liu, Changjie Chang, Dong-Yuan Zhan, Rui Zhao, Mingming Lam, Sin Man Shui, Guanghou Zhao, Ming-Hui Zheng, Lemin Chen, Min |
| Affiliation | Peking Univ, Peking Univ First Hosp, Div Renal, Dept Med,Inst Nephrol, Beijing, Peoples R China Peking Univ, Minist Educ, Key Lab Chron Kidney Dis Prevent & Treatment, Beijing, Peoples R China Chinese Acad Med Sci, Res Units Diag & Treatment Immune Mediated Kidn, Beijing, Peoples R China Inst Cardiovascular Sci, Inst Syst Biomed, Sch Basic Med Sci, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China Peking Univ, Beijing Key Lab Cardiovasc Receptors Res, Key Lab Cardiovasc Mol Biol & Regulatory Pept, Minist Hlth,Hlth Sci Ctr, Beijing, Peoples R China Peking Univ Third Hosp, Dept Cardiol, Beijing, Peoples R China Peking Univ Third Hosp, Inst Vasc Med, Beijing, Peoples R China Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing, Peoples R China Lipidall Technol Co Ltd, Changzhou, Jiangsu, Peoples R China Capital Med Univ, Beijing Tiantan Hosp, China Natl Clin Res Ctr Neurol Dis, Adv Innovat Ctr Human Brain Protect, Beijing, Peoples R China |
| Keywords | FATTY-ACID OXIDATION ACTIVATED-RECEPTOR-ALPHA PPAR-ALPHA SKELETAL-MUSCLE GENE-EXPRESSION KIDNEY AMPK CELLS MODEL MICE |
| Issue Date | Oct-2021 |
| Publisher | DIABETES |
| Abstract | Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. In this study, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA) and explore the association of ANXA1 with lipid accumulation in patients with DN. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion, and tubulointerstitial lesions in high-fat diet/streptozotocin-induced diabetic mice. ANXA1 deficiency promotes intrarenal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, ANXA1 silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated Thr(172) AMPK, resulting in decreased peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1b expression and increased HGPA-induced lipid accumulation, apoptosis, and elevated expression of proinflammatory and profibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of patients with DN. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression; hence, it holds great potential as a therapeutic target for DN. |
| URI | http://hdl.handle.net/20.500.11897/626566 |
| ISSN | 0012-1797 |
| DOI | 10.2337/db21-0050 |
| Indexed | SCI(E) |
| Appears in Collections: | 第一医院 第三医院 |
