Amelioration of neuropilin-1 and RAGE/matrix metalloproteinase-2 pathway-induced renal injury in diabetic rats by rosuvastatin

Authors

  • Rabia Nabi IIRC-5, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, U.P., India
  • Sahir Sultan Alvi IIRC-5, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, U.P., India https://orcid.org/0000-0002-5650-748X
  • Sultan Alouffi Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Saudi Arabia
  • Saif Khan Department of Basic Dental Sciences, College of Dental Sciences, University of Hail, Hail, Kingdom of Saudi Arabia
  • Adnan Ahmad IIRC-5, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, U.P., India
  • Mahvish Khan Department of Biology, College of Science, University of Hail, Hail, Kingdom of Saudi Arabia
  • Saheem Ahmad Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Saudi Arabia https://orcid.org/0000-0003-1215-0279
  • M. Salman Khan IIRC-5, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, U.P., India https://orcid.org/0000-0001-9716-8165

DOI:

https://doi.org/10.2298/ABS210316021N

Keywords:

rosuvastatin, neuropilin-1, AGE/RAGE-signaling, carboxymethyl-lysine, fluorogenic AGEs

Abstract

Paper description:

  • Alleviation of renal injury by rosuvastatin in streptozotocin-induced diabetes in rats was examined.
  • Rosuvastatin administration ameliorated plasma carboxymethyl-lysine (CML) and the renal fluorescent-advanced glycation end-product (AGE)
  • Transcription of RAGE, NFκB-2, TGF-β1 and MMP-2 was suppressed; the circulatory carbonyl content and paraoxonase-1 activity was ameliorated; renal histopathological features were attenuated, evidenced by improved glomerular appearance, Bowman’s space and abundant podocytes.
  • The presented mechanistic insight into the role of rosuvastatin in attenuating diabetes-mediated renal dysfunction shows that rosuvastatin prevented AGE-induced renal injury via stimulation of neuropilin-1 expression and AGE-receptor (RAGE)/matrix metalloproteinase-2 signaling.

Abstract: Advanced glycation end-products (AGEs) induce the production of reactive oxygen species (ROS) and extra cellular matrix (ECM) degradation via suppression of neuropilin-1 (NRP-1) and interaction with AGE-receptors (RAGE). This study aimed to reveal whether modulation of NRP-1 by rosuvastatin (RT) prevents AGE-induced renal injury via targeting RAGE/matrix metalloproteinase-2 (MMP-2) signaling in diabetic rats. Treatment with RT ameliorated the altered level of markers of glycemic control, renal injury, cholesterol, triglyceride (TG) and hepatic HMG-CoA reductase activity; the level of circulatory carboxymethyl-lysine (CML) and the accumulation of fluorogenic-AGEs in renal tissue was reduced; the expression of renal NRP-1, a checkpoint target, was stimulated; the transcription of RAGE, NFκB-2, TGF-β1 and MMP-2 was suppressed; the circulatory carbonyl content (CC) and paraoxonase-1 (PON-1) activity was ameliorated, and renal histopathological features were attenuated as evidenced by improved glomerular appearance, Bowman’s space and abundant podocytes in kidneys. In conclusion, RT exhibited the potential to counteract diabetes and AGE-induced renal pathologies via stimulation of NRP-1, suppression of RAGE, and of genes responsible for ECM disintegration (MMP-2) and the inflammatory response (NFκB-2).

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2021-07-13

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Nabi R, Alvi SS, Alouffi S, Khan S, Ahmad A, Khan M, Ahmad S, Khan MS. Amelioration of neuropilin-1 and RAGE/matrix metalloproteinase-2 pathway-induced renal injury in diabetic rats by rosuvastatin. Arch Biol Sci [Internet]. 2021Jul.13 [cited 2022Aug.7];73(2):265-78. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/6394

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