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El Tohamy M, Adel M, Rashad El-Menabawy F, Gad G E M, El-Gamal R, El Serougy H. Role of Cannabinoid Type 2 Receptor Activation in Renal Fibrosis Induced by Unilateral Ureteric Obstruction in Rats. rbmb.net 2023; 12 (1) :59-73
URL: http://rbmb.net/article-1-1097-en.html
URL: http://rbmb.net/article-1-1097-en.html
Mahmoud El Tohamy *, Mohamed Adel, Fayza Rashad El-Menabawy, Gad El Mawla Gad, Randa El-Gamal, Hanaa El Serougy
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt.
Abstract: (355 Views)
Background: Chronic kidney disease (CKD) ends mostly with renal fibrosis. The effect of CB2 receptor on renal fibrosis has been unclear. The aim of this study was to investigate the effect of CB2 receptor on renal fibrosis and the mechanisms behind it.
Methods: 50 adult male Sprague-Dawley rats were divided into 5 groups; normal, sham; rats had their ureters only manipulated, UUO; rats had their left ureters ligated, and JWH post; rats had their left ureters ligated and they received JWH 133 for 14 days, JWH pre+post; rats received JWH 133 for 14 days before and after UUO procedure. Serum creatinine and BUN were assessed together with tissue MDA, GSH, and catalase. Histopathological evaluation of the renal tissue by H&E and Masson’s trichrome was done. Immunohistochemical staining for TGF-β1, AQP1, Caspase-3, LC3B and p62 was performed. AQP1 and CB2 receptors genes expression was detected by quantitative RT-PCR.
Results: UUO had caused severe damage in the renal tissue with reduction of the renal function parameter accompanied by increase in the collagen deposition with increase TGF-β1 and decrease AQP1 expression.
Conclusions: The improvement of these parameters with JWH-133 suggests an anti-fibrotic role of CB2 receptor activation through reduction of oxidative stress, apoptosis, and autophagy.
Methods: 50 adult male Sprague-Dawley rats were divided into 5 groups; normal, sham; rats had their ureters only manipulated, UUO; rats had their left ureters ligated, and JWH post; rats had their left ureters ligated and they received JWH 133 for 14 days, JWH pre+post; rats received JWH 133 for 14 days before and after UUO procedure. Serum creatinine and BUN were assessed together with tissue MDA, GSH, and catalase. Histopathological evaluation of the renal tissue by H&E and Masson’s trichrome was done. Immunohistochemical staining for TGF-β1, AQP1, Caspase-3, LC3B and p62 was performed. AQP1 and CB2 receptors genes expression was detected by quantitative RT-PCR.
Results: UUO had caused severe damage in the renal tissue with reduction of the renal function parameter accompanied by increase in the collagen deposition with increase TGF-β1 and decrease AQP1 expression.
Conclusions: The improvement of these parameters with JWH-133 suggests an anti-fibrotic role of CB2 receptor activation through reduction of oxidative stress, apoptosis, and autophagy.
Type of Article: Original Article |
Subject:
Cell Biology
Received: 2022/11/17 | Accepted: 2023/01/22 | Published: 2023/08/15
Received: 2022/11/17 | Accepted: 2023/01/22 | Published: 2023/08/15
References
1. Shawky SA, Gaber O, Mostafa E, Sarhan WM. Uncoupling Protein 2 Expression Modulates Obesity in Chronic Kidney Disease Patients. Rep Biochem Mol Biol. 2021;10(1):119-25. [DOI:10.52547/rbmb.10.1.119] [PMID] [PMCID]
2. Zhao HY, Li HY, Jin J, Jin JZ, Zhang LY, Xuan MY, et al. L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. Korean J Intern Med. 2021;36(Suppl 1):S180. [DOI:10.3904/kjim.2019.413] [PMID] [PMCID]
3. Grande MT, Pérez-Barriocanal F, López-Novoa JM. Role of inflammation in tubulo-interstitial damage associated to obstructive nephropathy. J Inflamm (Lond). 2010;7(1):19. [DOI:10.1186/1476-9255-7-19] [PMID] [PMCID]
4. Tam J. The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases. J Basic Clin Physiol Pharmacol. 2016;27(3):267-76. [DOI:10.1515/jbcpp-2015-0055] [PMID]
5. Lu H-C, Mackie K. An introduction to the endogenous cannabinoid system. Biol Psychiatry. 2016;79(7):516-25. [DOI:10.1016/j.biopsych.2015.07.028] [PMID] [PMCID]
6. Parastouei K, Aarabi MH, Hamidi GA, Nasehi Z, Kabiri-Arani S, Jozi F, et al. A CB2 Receptor Agonist Reduces the Production of Inflammatory Mediators and Improves Locomotor Activity in Experimental Autoimmune Encephalomyelitis. Rep Biochem Mol Biol. 2022;11(1):1-9. [DOI:10.52547/rbmb.11.1.1] [PMID] [PMCID]
7. Zhou L, Zhou S, Yang P, Tian Y, Feng Z, Xie X-Q, et al. Targeted inhibition of the type 2 cannabinoid receptor is a novel approach to reduce renal fibrosis. Kidney Int. 2018;94(4):756-72. [DOI:10.1016/j.kint.2018.05.023] [PMID] [PMCID]
8. Barutta F, Corbelli A, Mastrocola R, Gambino R, Di Marzo V, Pinach S, et al. Cannabinoid receptor 1 blockade ameliorates albuminuria in experimental diabetic nephropathy. Diabetes. 2010;59(4):1046-54. [DOI:10.2337/db09-1336] [PMID] [PMCID]
9. Çakır M, Tekin S, Doğanyiğit Z, Çakan P, Kaymak E. The protective effect of cannabinoid type 2 receptor activation on renal ischemia-reperfusion injury. Mol Cell Biochem. 2019:1-10. [DOI:10.1007/s11010-019-03616-6] [PMID]
10. Swanson ML, Regner KR, Moore BM, Park F. Cannabinoid Type 2 Receptor Activation Reduces the Progression of Kidney Fibrosis Using a Mouse Model of Unilateral Ureteral Obstruction. Cannabis Cannabinoid Res. 2022. [DOI:10.1089/can.2021.0127] [PMID]
11. Tan Q, Chen Q, Feng Z, Shi X, Tang J, Tao Y, et al. Cannabinoid receptor 2 activation restricts fibrosis and alleviates hydrocephalus after intraventricular hemorrhage. Brain Res. 2017;1654:24-33. [DOI:10.1016/j.brainres.2016.10.016] [PMID]
12. Yang C-Y, Chau Y-P, Chen A, Lee OK-S, Tarng D-C, Yang A-H. Targeting cannabinoid signaling for peritoneal dialysis-induced oxidative stress and fibrosis. World J Nephrol. 2017;6(3):111. [DOI:10.5527/wjn.v6.i3.111] [PMID] [PMCID]
13. Dhopeshwarkar A, Mackie K. CB2 Cannabinoid receptors as a therapeutic target-what does the future hold? Mol Pharmacol. 2014;86(4):430-7. [DOI:10.1124/mol.114.094649] [PMID] [PMCID]
14. Figueroa SM, Lozano M, Lobos C, Hennrikus MT, Gonzalez AA, Amador CA. Upregulation of Cortical Renin and Downregulation of Medullary (Pro) Renin Receptor in Unilateral Ureteral Obstruction. Front Pharmacol. 2019;10:1314. [DOI:10.3389/fphar.2019.01314] [PMID] [PMCID]
15. Shi Z, Wang Q, Zhang Y, Jiang D. Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model. Stem Cell Res Ther. 2020;11(1):1-21. [DOI:10.1186/s13287-020-01767-8] [PMID] [PMCID]
16. Panel BBR. Guidelines for safe work practices in human and animal medical diagnostic laboratories. MMWR Suppl. 2012;61:357-63.
17. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671-5. [DOI:10.1038/nmeth.2089] [PMID] [PMCID]
18. Freeman TC, Lee K, Richardson PJ. Analysis of gene expression in single cells. Current opinion in biotechnology. 1999;10(6):579-82. [DOI:10.1016/S0958-1669(99)00036-1] [PMID]
19. Bouley R, Palomino Z, Tang S-S, Nunes P, Kobori H, Lu HA, et al. Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression. Am J Physiol Renal Physiol. 2009;297(6):F1575-F86. [DOI:10.1152/ajprenal.90762.2008] [PMID] [PMCID]
20. Zhang M, Shi X, Wu J, Wang Y, Lin J, Zhao Y, et al. CoCl2 induced hypoxia enhances osteogenesis of rat bone marrow mesenchymal stem cells through cannabinoid receptor 2. Arch Oral Biol. 2019;108:104525. [DOI:10.1016/j.archoralbio.2019.104525] [PMID]
21. Lai KN, Leung JC, Chan LY, Saleem MA, Mathieson PW, Tam KY, et al. Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy. Nephrol Dial Transplant. 2009;24(1):62-72. [DOI:10.1093/ndt/gfn441] [PMID]
22. Nogueira A, Pires MJ, Oliveira PA. Pathophysiological mechanisms of renal fibrosis: a review of animal models and therapeutic strategies. in vivo. 2017;31(1):1-22. [DOI:10.21873/invivo.11019] [PMID] [PMCID]
23. Zhao D, Luan Z. Oleanolic acid attenuates renal fibrosis through TGF-β/Smad pathway in a rat model of unilateral ureteral obstruction. Evid Based Complement Alternat Med 2020;2020. [DOI:10.1155/2020/2085303] [PMID] [PMCID]
24. Chaabane W, Praddaude F, Buleon M, Jaafar A, Vallet M, Rischmann P, et al. Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO). Am J Physiol Renal Physiol. 2013;304(4):F432-F9. [DOI:10.1152/ajprenal.00425.2012] [PMID]
25. Barutta F, Grimaldi S, Franco I, Bellini S, Gambino R, Pinach S, et al. Deficiency of cannabinoid receptor of type 2 worsens renal functional and structural abnormalities in streptozotocin-induced diabetic mice. Kidney Int. 2014;86(5):979-90. [DOI:10.1038/ki.2014.165] [PMID]
26. Mukhopadhyay P, Baggelaar M, Erdelyi K, Cao Z, Cinar R, Fezza F, et al. The novel, orally available and peripherally restricted selective cannabinoid CB2 receptor agonist LEI‐101 prevents cisplatin‐induced nephrotoxicity. Br J Pharmacol. 2016;173(3):446-58. [DOI:10.1111/bph.13338] [PMID] [PMCID]
27. Çakır M, Tekin S, Doğanyiğit Z, Çakan P, Kaymak E. The protective effect of cannabinoid type 2 receptor activation on renal ischemia-reperfusion injury. Mol Cell Biochem. 2019;462. [DOI:10.1007/s11010-019-03616-6] [PMID]
28. Mukhopadhyay P, Pan H, Rajesh M, Bátkai S, Patel V, Harvey‐White J, et al. CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model. Br J Pharmacol. 2010;160(3):657-68. [DOI:10.1111/j.1476-5381.2010.00769.x] [PMID] [PMCID]
29. Wang Z-Y, Wang P, Bjorling DE. Treatment with a cannabinoid receptor 2 agonist decreases severity of established cystitis. J Urol. 2014;191(4):1153-8. [DOI:10.1016/j.juro.2013.10.102] [PMID] [PMCID]
30. Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-β signaling in fibrosis. Growth Factors. 2011;29(5):196-202. [DOI:10.3109/08977194.2011.595714] [PMID] [PMCID]
31. Correia‐Sá I, Carvalho C, A. Machado V, Carvalho S, Serrão P, Marques M, et al. Targeting cannabinoid receptor 2 (CB2) limits collagen production-An in vitro study in a primary culture of human fibroblasts. Fundam Clin Pharmacol. 2022;36(1):89-99. [DOI:10.1111/fcp.12716] [PMID]
32. Lecru L, Desterke C, Grassin-Delyle S, Chatziantoniou C, Vandermeersch S, Devocelle A, et al. Cannabinoid receptor 1 is a major mediator of renal fibrosis. Kidney Int. 2015;88(1):72-84. [DOI:10.1038/ki.2015.63] [PMID]
33. Muñoz-Luque J, Ros J, Fernández-Varo G, Tugues S, Morales-Ruiz M, Alvarez CE, et al. Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats. J Pharmacol Exp Ther. 2008;324(2):475-83. [DOI:10.1124/jpet.107.131896] [PMID] [PMCID]
34. Du W, Zhang T, Yang F, Gul A, Tang Z, Zhang H, et al. Endocannabinoid signalling/cannabinoid receptor 2 is involved in icariin-mediated protective effects against bleomycin-induced pulmonary fibrosis. Phytomedicine. 2022:154187. [DOI:10.1016/j.phymed.2022.154187] [PMID]
35. Li J, Zhang M, Mao Y, Li Y, Zhang X, Peng X, et al. The potential role of aquaporin 1 on aristolochic acid I induced epithelial mesenchymal transition on HK‐2 cells. J Cell Physiol. 2018;233(6):4919-25. [DOI:10.1002/jcp.26310] [PMID]
36. Tao Y, Tang J, Chen Q, Guo J, Li L, Yang L, et al. Cannabinoid CB2 receptor stimulation attenuates brain edema and neurological deficits in a germinal matrix hemorrhage rat model. Brain Res. 2015;1602:127-35. [DOI:10.1016/j.brainres.2015.01.025] [PMID]
37. Esposito G, De Filippis D, Maiuri MC, De Stefano D, Carnuccio R, Iuvone T. Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in β-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-κB involvement. Neurosci Lett. 2006;399(1-2):91-5. [DOI:10.1016/j.neulet.2006.01.047] [PMID]
38. Katunuma N, Matsui A, Le Q, Utsumi K, Salvesen G, Ohashi A. Novel procaspase- 3 activating cascade mediated by lysoapoptases and its biological significances in apoptosis. Adv Enzyme Regul. 2001;41(1):237-50. [DOI:10.1016/S0065-2571(00)00018-2] [PMID]
39. Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, et al. A ubiquitin-like system mediates protein lipidation. Nature. 2000;408(6811):488-92. [DOI:10.1038/35044114] [PMID]
40. Pircs K, Nagy P, Varga A, Venkei Z, Erdi B, Hegedus K, et al. Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila. PLoS One. 2012. [DOI:10.1371/journal.pone.0044214] [PMID] [PMCID]
41. Forbes MS, Thornhill BA, Chevalier RL. Proximal tubular injury and rapid formation of atubular glomeruli in mice with unilateral ureteral obstruction: a new look at an old model. Am J Physiol Renal Physiol. 2011;301(1):F110-F7. [DOI:10.1152/ajprenal.00022.2011] [PMID] [PMCID]
42. Livingston MJ, Ding H-F, Huang S, Hill JA, Yin X-M, Dong Z. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction. Autophagy. 2016;12(6):976-98. [DOI:10.1080/15548627.2016.1166317] [PMID] [PMCID]
43. Ding Y, ll Kim S, Lee S-Y, Koo JK, Wang Z, Choi ME. Autophagy regulates TGF-β expression and suppresses kidney fibrosis induced by unilateral ureteral obstruction. J Am Soc Nephrol. 2014;25(12):2835-46. [DOI:10.1681/ASN.2013101068] [PMID] [PMCID]
44. Liu A, Yuan Q, Zhang B, Yang L, He Q, Chen K, et al. Cannabinoid receptor 2 activation alleviates septic lung injury by promoting autophagy via inhibition of inflammatory mediator release. Cell Signal. 2020;69:109556. [DOI:10.1016/j.cellsig.2020.109556] [PMID]
45. Liu W, Chen C, Gu X, Zhang L, Mao X, Chen Z, et al. AM1241 alleviates myocardial ischemia-reperfusion injury in rats by enhancing Pink1/Parkin-mediated autophagy. Life Sci. 2021;272:119228. [DOI:10.1016/j.lfs.2021.119228] [PMID]
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