title: Therapy with a Selective Cannabinoid Receptor Type 2 Agonist Limits Albuminuria and Renal Injury in Mice with Type 2 Diabetic Nephropathy.
abstract: OBJECTIVE
  A critical involvement of the endocannabinoid/cannabinoid receptor system in diabetes and its complications has been recognized. Experimental evidence suggested that activation of the cannabinoid receptor type 2 (CB2), which is expressed in the kidney by podocytes and inflammatory cells, had a protective role in early streptozotocin-induced type 1 diabetes in mice. No experimental evidence is so far available on the effects of CB2 agonists in type 2 diabetes. In this study, we investigated the effects of a CB2 agonist given at a phase of overt disease on renal functional and structural changes in BTBR ob/ob mice, a model of type 2 diabetic nephropathy.
  
  
  METHODS
  BTBR ob/ob mice received, from 10 to 21 weeks of age, vehicle, the selective CB2 agonist HU910, or lisinopril used as standard therapy for comparison. BTBR wild-type mice served as controls.
  
  
  RESULTS
  Treatment with CB2 agonist reduced progressive albuminuria of BTBR ob/ob mice to a similar extent as ACE inhibitor. The antiproteinuric effect of CB2 agonist was associated with the amelioration of the defective nephrin expression in podocytes of diabetic mice. CB2 agonist limited mesangial matrix expansion, fibronectin accumulation and sclerosis. Glomerular infiltration of Mac-2-positive monocytes/machrophages was attenuated by CB2 agonist, at least in part due to the drug's ability to reduce MCP-1 chemotactic signals. Renoprotective effects of CB2 were similar to those achieved by ACE inhibitor.
  
  
  CONCLUSIONS
  These results suggest that CB2 agonism is a potential option to be added to the available therapeutic armamentarium for type 2 diabetic nephropathy.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors.forename: Carlamaria
authors.initials: C
authors.lastname: Zoja
authors.forename: Monica
authors.initials: M
authors.lastname: Locatelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Corna
authors.forename: Sebastian
authors.initials: S
authors.lastname: Villa
authors.forename: Daniela
authors.initials: D
authors.lastname: Rottoli
authors.forename: Valeria
authors.initials: V
authors.lastname: Nava
authors.forename: Roberta
authors.initials: R
authors.lastname: Verde
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Juergen
authors.initials: J
authors.lastname: Fingerle
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Adam
authors.forename: Benno
authors.initials: B
authors.lastname: Rothenhaeusler
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ottaviani
authors.forename: Agnes
authors.initials: A
authors.lastname: Bénardeau
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
mesh_terms: D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use*; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003929:Diabetic Neuropathies / Q000150:complications* / Q000473:pathology; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D050199:Podocytes / Q000473:pathology; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*
chemical_list: D001786:Blood Glucose; D001643:Bridged Bicyclo Compounds; D063386:Cannabinoid Receptor Agonists; C573862:HU-910; D043885:Receptor, Cannabinoid, CB2