• Open Access

Molecular events in matrix protein metabolism in the aging kidney

Authors

  • Kavithalakshmi Sataranatarajan,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    2. The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USA
    Search for more papers by this author
  • Denis Feliers,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    Search for more papers by this author
  • Meenalakshmi M. Mariappan,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    2. South Texas Veterans Health Care System, San Antonio, TX, USA
    Search for more papers by this author
  • Hak Joo Lee,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    2. South Texas Veterans Health Care System, San Antonio, TX, USA
    Search for more papers by this author
  • Myung Ja Lee,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    Search for more papers by this author
  • Robert T. Day,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    Search for more papers by this author
  • Hima Bindu Yalamanchili,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    Search for more papers by this author
  • Goutam G. Choudhury,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    2. South Texas Veterans Health Care System, San Antonio, TX, USA
    3. Geriatric Research, Education and Clinical Center, San Antonio, TX, USA
    Search for more papers by this author
  • Jeffrey L. Barnes,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    2. South Texas Veterans Health Care System, San Antonio, TX, USA
    Search for more papers by this author
  • Holly Van Remmen,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    2. The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USA
    3. Geriatric Research, Education and Clinical Center, San Antonio, TX, USA
    Search for more papers by this author
  • Arlan Richardson,

    1. Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    2. The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USA
    3. Geriatric Research, Education and Clinical Center, San Antonio, TX, USA
    Search for more papers by this author
  • Balakuntalam S. Kasinath

    Corresponding author
    1. The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USA
    2. South Texas Veterans Health Care System, San Antonio, TX, USA
    • Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
    Search for more papers by this author

Correspondence

Balakuntalam S. Kasinath, Department of Medicine, MC7882, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio TX 78229-3900, USA. Tel.: 210 567 4707; fax: 210 567 4712; e-mail: kasinath@uthscsa.edu

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.

Ancillary