title: Establishment of an inflamed animal model of diabetic nephropathy.
abstract: OBJECTIVE
  Inflammatory stress plays a crucial role in the progression of diabetic nephropathy (DN). This study aimed to establish a novel inflamed animal model of DN and to evaluate its significance in DN.
  
  
  METHODS
  Nondiabetic db/m mice and diabetic db/db mice were randomly divided into four groups: db/m, db/m+casein, db/db, and db/db+casein for eight weeks. Casein was subcutaneously injected to induce chronic inflammation. Body weight and albumin to creatinine ratio (ACR) in the urine were measured every week. The plasma levels of serum amyloid protein A (SAA) and tumour necrotic factor-α (TNF-α) were determined with the enzyme-linked immunosorbent assay. The morphological changes to the renal pathology and ultra-microstructures were checked by pathological staining and electron microscopy. Immunofluorescent staining and Western blotting were used to determine the protein expression of podocyte-specific molecules and inflammatory cytokines in kidneys.
  
  
  RESULTS
  ACR, plasma levels of SAA and TNF-α, protein expression of inflammatory cytokines, mesangial expansion, collagen accumulation, and foot process effacement in kidneys of casein-injected db/db mice were significantly increased compared with the db/db mice. Casein injection markedly decreased the protein expression of Wilms' tumor-1 and nephrin in kidneys of db/db mice, which are specific podocyte biomarkers, suggesting that chronic inflammation accelerates podocyte injuries in db/db mice. Interestingly, no obvious urinary protein, inflammatory cytokine expression, or histological changes in the kidneys of casein-injected db/m mice were found compared with the db/m mice.
  
  
  CONCLUSIONS
  An inflamed animal model of DN was successfully established and may provide a useful tool for investigating the pathogenesis of DN under inflammatory stress.
authors: 1. Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.
authors: Kun Ling
authors: KL
authors: Ma
authors: 1. Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.
authors: Yang
authors: Y
authors: Zhang
authors: 1. Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.
authors: Jing
authors: J
authors: Liu
authors: 1. Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.
authors: Yu
authors: Y
authors: Wu
authors: 1. Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.
authors: Ze Bo
authors: ZB
authors: Hu
authors: 2. Centre for Nephrology, University College London (UCL) Medical School, Royal Free Campus, UK.
authors: Xiong Zhong
authors: XZ
authors: Ruan
authors: 1. Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.
authors: Bi Cheng
authors: BC
authors: Liu
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000150:complications / Q000473:pathology*; D004195:Disease Models, Animal; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011507:Proteinuria / Q000150:complications
keywords: Diabetic nephropathy; animal model; db/db mice; inflammation