Comparison of Glomerular and Podocyte mRNA Profiles in Streptozotocin-Induced Diabetes.
Evaluating the mRNA profile of podocytes in the diabetic kidney may indicate genes involved in the pathogenesis of diabetic nephropathy. To determine if the podocyte-specific gene information contained in mRNA profiles of the whole glomerulus of the diabetic kidney accurately reflects gene expression in the isolated podocytes, we crossed Nos3(-/-) IRG mice with podocin-rtTA and TetON-Cre mice for enhanced green fluorescent protein labeling of podocytes before diabetic injury. Diabetes was induced by streptozotocin, and mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice were examined 10 weeks later. Expression of podocyte-specific markers in glomeruli was downregulated in diabetic mice compared with controls. However, expression of these markers was not altered in sorted podocytes from diabetic mice. When mRNA levels of glomeruli were corrected for podocyte number per glomerulus, the differences in podocyte marker expression disappeared. Analysis of the differentially expressed genes in diabetic mice also revealed distinct upregulated pathways in the glomeruli (mitochondrial function, oxidative stress) and in podocytes (actin organization). In conclusion, our data suggest reduced expression of podocyte markers in glomeruli is a secondary effect of reduced podocyte number, thus podocyte-specific gene expression detected in the whole glomerulus may not represent that in podocytes in the diabetic kidney.
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China;
Jia
J
Fu
Division of Nephrology, Department of Medicine.
Chengguo
C
Wei
Division of Nephrology, Department of Medicine.
Kyung
K
Lee
Division of Nephrology, Department of Medicine.
Weijia
W
Zhang
Flow Cytometry Shared Resource Facility, Icahn School of Medicine at Mount Sinai, New York; and.
Wu
W
He
Division of Nephrology, Department of Medicine.
Peter
P
Chuang
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; cijiang.he@mssm.edu zhihong-liu@hotmail.com.
Zhihong
Z
Liu
Division of Nephrology, Department of Medicine, Renal Program, James J. Peters VA Medical Center at Bronx, New York. cijiang.he@mssm.edu zhihong-liu@hotmail.com.
John Cijiang
JC
He
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D050199:Podocytes / Q000737:chemistry* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis*
D012333:RNA, Messenger
diabetic nephropathy; gene transcription; glomerulus; podocyte; signaling