Journal Articles

Proteinuria in Cynomolgus macaques (Macaca fascicularis) with Spontaneously Developed Metabolic Disorder and Diabetes: Transcriptome Analysis of Biopsy Kidney

February 03, 2015

Proteinuria in Cynomolgus macaques (Macaca fascicularis) with Spontaneously Developed Metabolic Disorder and Diabetes: Transcriptome Analysis of Biopsy Kidney ,  Journal of Diabetes and Metabolism. Sheng Guo1, Wubin Qian1, Fenglai Du1, Bingdi Wang1, Xiaoli Wang1, Yupeng Fang1, Xuan Chen1, Michael Benzinou1, Francine M. Gregoire2, Michael, Staup2, Keefe Chng2, Yaxiong Chen1, Yong-Fu Xiao1, Yi-Xin (Jim) Wang1,2*

1Cardiovascular and Metabolic Diseases Research, Crown Bioscience Bioscience Inc. Taicang, Jiangsu Province, China
2David H. Murdock Research Institute, Kannapolis, USA

Abstract
Although Type 2 Diabetes Mellitus (T2DM) is well characterized Non-Human Primate (NHP), the phenotypes
of diabetic nephropathy, and its molecular mechanisms are not well studied in NHPs. Diabetic nephropathy in
cynomolgus macaques with spontaneous dysmetabolism (Pre-DM, n=19) and diabetes (DM, n=20) were compared
with normal controls (N, n=11). There were 9 NHPs with albuminuria (>42 mg/day) in the DM (45%), only 1 in
Pre-DM and none in N group. The renal function measured by estimated glomerular filtration rate (eGFR) was not
significantly different among the 3 groups, indicating that these NHPs were in an early stage of renal disease. From
these NHPs, 3 N, 3 Pre-DM without albuminuria and 6 DM with albuminuria were selected for transcriptome analysis
of kidney biopsies. There were 95 differentially expressed genes (DEGs) detected amongst the 3 groups, of which,
75DEGs between the N and DM related to diabetic nephropathy; 66 DEGs between the N and Pre-DM related to
dysmetabolism without nephropathy; 68 DEGs between N and both Pre-DM & DM related to dsymetabolism; but only
1 nephropathy specific gene (LCT lactase) between the DM with albuminuria (DM) and Pre-DM without albuminuria;
only 4 DEGs between the DM with albuminuria and both N & Pre-DM without albuminuria specific to nephropathy.
Signaling pathway analysis of the relevant DEGs and encoded proteins highlighted the role of a kidney failure, renal
and urological diseases, and inflammatory diseases related network, in which the most pivotal gene in this network
is Tumor Necrosis Factor (TNF), indicating that nephropathy is a disease closely related to inflammation and cell
death. Thus, the present study was the first detailed characterization of the diabetic nephropathy phenotypes and
the kidney histopathological changes in NHPs and provided molecular insights into novel mechanisms of disease
progression, potential new drug targets as well as specific diagnostic biomarkers.

 

 

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