Anti-Inflammatory Effects of Ang-(1-7) in Ameliorating HFD-Induced Renal Injury through LDLr-SREBP2-SCAP Pathway.
The angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis (ACE2-Ang-(1-7)-Mas axis) is reported to participate in lipid metabolism in kidney, but its precise effects and underlying mechanisms remain unknown. We hypothesized that Ang-(1-7) reduces lipid accumulation and improves renal injury through the low density lipoprotein receptor-sterol regulatory element binding proteins 2-SREBP cleavage activating protein (LDLr-SREBP2-SCAP) system by suppressing inflammation in high fat diet (HFD)-fed mice. In this study, male C57BL/6 mice were randomized into four groups: STD (standard diet)+saline, HFD+saline, HFD+Ang-(1-7) and STD+Ang-(1-7). After 10 weeks of feeding, mice were administered Ang-(1-7) or saline for two weeks. We found that high inflammation status induced by HFD disrupted the LDLr-SREBP2-SCAP feedback system. Treatment of mice fed a high-fat diet with Ang-(1-7) induced significant improvement in inflammatory status, following the downregulation of LDLr, SREBP2 and SCAP, and then, decreased lipid deposition in kidney and improved renal injury. In conclusion, the anti-inflammatory effect of Ang-(1-7) alleviates renal injury triggered by lipid metabolic disorders through a LDLr- SREBP2-SCAP pathway.
Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Yaning
Y
Zheng
Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Lin
L
Tang
Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Wenhan
W
Huang
Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Ruyu
R
Yan
Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Feifeng
F
Ren
Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Lei
L
Luo
Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Ling
L
Zhang
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D000803:Angiotensin I / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects*; D050171:Dyslipidemias / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D051782:Sterol Regulatory Element Binding Protein 2 / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D010446:Peptide Fragments; D011973:Receptors, LDL; D051782:Sterol Regulatory Element Binding Protein 2; D000803:Angiotensin I; C118790:angiotensin I (1-7)