The possible involvement of tensin2 in the expression and extension of nephrin by glomerular podocytes in mice.
The prevalence of chronic kidney disease (CKD) is increasing worldwide and proteinuria is a critical prognostic indicator of CKD. Nephrin is produced by podocytes and functions as a slit barrier for inhibition of proteinuria. Nephrin expression is frequently decreased in CKD patients. Nevertheless, the mechanism by which nephrin declines during CKD-related pathological states remains to be determined. Using tensin2-deficient mice (ICGN/Oa strain), we provide evidence that tensin2 is important for glomerular nephrin expression in vivo. In heterozygous mice with a single mutated tensin2 allele, nephrin expression was maintained, while albuminuria was not observed. In contrast, nephrin expression was impaired, especially in the central zones of glomeruli of homozygous mice (with double mutated tensin2 alleles), even at one week after birth. In homozygous mice, extension of synaptopodin, a key actin-associated protein, was also suppressed in the central zone of glomerular tufts. Consistent with the loss of nephrin and synaptopodin expression, severe albuminuria was detected in homozygous ICGN/Oa mice. Therefore, we suggested that tensin2 is involved in expression and extension of nephrin, while tensin2 deficiency may result in proteinuria, associated with the loss of slit integrity.
Kato
Takashi
T
Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Mizuno
Shinya
S
Taketo
Makoto Mark
MM
Kurosawa
Tsutomu Miki
TM
D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D000070876:Tensins
D008565:Membrane Proteins; D008840:Microfilament Proteins; C503968:Synpo protein, mouse; D000070876:Tensins; C113267:nephrin; D010749:Phosphoprotein Phosphatases; C511707:Tns2 protein, mouse