Molecular events in matrix protein metabolism in the aging kidney

Aging Cell

Kavithalakshmi Sataranatarajan¹  Denis Feliers¹  Meenalakshmi M. Mariappan¹  Hak Joo Lee¹  Myung Ja Lee¹  Robert T. Day¹  Hima Bindu Yalamanchili¹  Goutam G. Choudhury¹  Jeffrey L. Barnes¹  Holly Van Remmen¹  Arlan Richardson¹ 

[1] Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA

关键词: albuminuria;    collagen;    fibrosis;    microRNAs;    SMAD3;    TGF beta;   

DOI  :  10.1111/acel.12008

来源: Wiley

【 摘 要 】

Summary

We explored molecular events associated with aging-induced matrix changes in the kidney. C57BL6 mice were studied in youth, middle age, and old age. Albuminuria and serum cystatin C level (an index of glomerular filtration) increased with aging. Renal hypertrophy was evident in middle-aged and old mice and was associated with glomerulomegaly and increase in mesangial fraction occupied by extracellular matrix. Content of collagen types I and III and fibronectin was increased with aging; increment in their mRNA varied with the phase of aging. The content of ZEB1 and ZEB2, collagen type I transcription inhibitors, and their binding to the collagen type Iα2 promoter by ChIP assay also showed age-phase-specific changes. Lack of increase in mRNA and data from polysome assay suggested decreased degradation as a potential mechanism for kidney collagen type I accumulation in the middle-aged mice. These changes occurred with increment in TGFβ mRNA and protein and activation of its SMAD3 pathway; SMAD3 binding to the collagen type Iα2 promoter was also increased. TGFβ-regulated microRNAs (miRs) exhibited selective regulation. The renal cortical content of miR-21 and miR-200c, but not miR-192, miR-200a, or miR-200b, was increased with aging. Increased miR-21 and miR-200c contents were associated with reduced expression of their targets, Sprouty-1 and ZEB2, respectively. These data show that aging is associated with complex molecular events in the kidney that are already evident in the middle age and progress to old age. Age-phase-specific regulation of matrix protein synthesis occurs and involves matrix protein–specific transcriptional and post-transcriptional mechanisms.

【 授权许可】

Unknown   
© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland