Molecular events in matrix protein metabolism in the aging kidney

Kavithalakshmi Sataranatarajan, Denis Feliers, Meenalakshmi M. Mariappan, Hak Joo Lee, Myung Ja Lee, Robert T. Day, Hima Bindu Yalamanchili, Goutam Ghosh-choudhury, Jeffrey L. Barnes, Holly Van Remmen, Arlan Richardson, Balakuntalam S Kasinath

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1065-1073
Number of pages9
JournalAging Cell
Volume11
Issue number6
DOIs
StatePublished - Dec 2012

Fingerprint

Kidney
Collagen Type I
Proteins
Messenger RNA
Collagen
Cystatin C
Albuminuria
Collagen Type III
Polyribosomes
MicroRNAs
Fibronectins
Hypertrophy
Extracellular Matrix
Serum

Keywords

  • Albuminuria
  • Collagen
  • Fibrosis
  • MicroRNAs
  • SMAD3
  • TGF beta

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Sataranatarajan, K., Feliers, D., Mariappan, M. M., Lee, H. J., Lee, M. J., Day, R. T., ... Kasinath, B. S. (2012). Molecular events in matrix protein metabolism in the aging kidney. Aging Cell, 11(6), 1065-1073. https://doi.org/10.1111/acel.12008

Molecular events in matrix protein metabolism in the aging kidney. / Sataranatarajan, Kavithalakshmi; Feliers, Denis; Mariappan, Meenalakshmi M.; Lee, Hak Joo; Lee, Myung Ja; Day, Robert T.; Yalamanchili, Hima Bindu; Ghosh-choudhury, Goutam; Barnes, Jeffrey L.; Van Remmen, Holly; Richardson, Arlan; Kasinath, Balakuntalam S.

In: Aging Cell, Vol. 11, No. 6, 12.2012, p. 1065-1073.

Research output: Contribution to journalArticle

Sataranatarajan, K, Feliers, D, Mariappan, MM, Lee, HJ, Lee, MJ, Day, RT, Yalamanchili, HB, Ghosh-choudhury, G, Barnes, JL, Van Remmen, H, Richardson, A & Kasinath, BS 2012, 'Molecular events in matrix protein metabolism in the aging kidney', Aging Cell, vol. 11, no. 6, pp. 1065-1073. https://doi.org/10.1111/acel.12008
Sataranatarajan K, Feliers D, Mariappan MM, Lee HJ, Lee MJ, Day RT et al. Molecular events in matrix protein metabolism in the aging kidney. Aging Cell. 2012 Dec;11(6):1065-1073. https://doi.org/10.1111/acel.12008
Sataranatarajan, Kavithalakshmi ; Feliers, Denis ; Mariappan, Meenalakshmi M. ; Lee, Hak Joo ; Lee, Myung Ja ; Day, Robert T. ; Yalamanchili, Hima Bindu ; Ghosh-choudhury, Goutam ; Barnes, Jeffrey L. ; Van Remmen, Holly ; Richardson, Arlan ; Kasinath, Balakuntalam S. / Molecular events in matrix protein metabolism in the aging kidney. In: Aging Cell. 2012 ; Vol. 11, No. 6. pp. 1065-1073.
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