Intraperitoneal administration of the globular adiponectin gene ameliorates diabetic nephropathy in Wistar rats.
The present study investigated the potential effects of the long-term expression of exogenous adiponectin (ADPN) on normal and diabetic kidneys. Type 2 diabetes mellitus models were induced by high-lipid and high-sucrose feeding plus intraperitoneal injection of streptozotocin. The recombinant plasmid pIRES2-EGFP-gAd, which is able to co-express globular ADPN (gAd) and enhanced green fluorescent protein (EGFP), was intraperitoneally injected into rat models mediated by Lipofectamine. In total, 32 Wistar rats were randomly assigned into four groups: the normal control group, the diabetes group, the diabetes group treated with pIRES2-EGFP-gAd and the diabetes group treated with pIRES2-EGFP. After 12 weeks, serum biochemistry and urine albumin levels were measured. The kidneys were collected to assess the generation of reactive oxygen species (ROS) and the renal pathological changes were observed by light microcopy. The protein expression of endothelial nitric oxide synthase (eNOS), transforming growth factor-β1 (TGF-β1) and phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were determined by an immunohistochemical staining method and western blot analysis. Intraperitoneal injection of the human gAd gene via Lipofectamine resulted in abundant ADPN protein in the kidney. In the diabetic rats, the delivery of the exogenous gAd gene ameliorated the progression of diabetic nephropathy (DN). ADPN attenuated urine albumin excretion in the diabetic rats. ADPN also mitigated glomerular mesangial expansion, reduced the generation of ROS and prevented interstitial fibrosis. In addition, the expression of gAd inhibited the renal expression of TGF-β1, promoted the protein expression of eNOS and activated the opening of the AMPK signaling pathway in the renal tissues of the diabetic rats. Despite the effects of ADPN on DN being controversial, these observations indicate that the supplementation of ADPN is beneficial in ameliorating DN in rats.
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Fang
F
Yuan
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Ying-Hong
YH
Liu
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Fu-You
FY
Liu
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
You-Ming
YM
Peng
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Jun-Wei
JW
Tian
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000628:therapy; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011507:Proteinuria / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism / Q000652:urine
D052242:Adiponectin; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases