Collagen-binding proteins in age-dependent changes in renal collagen turnover: microarray analysis of mRNA expression

Abstract

Hultström M, Leh S, Paliege A, Bachmann S, Skogstrand T, Iversen BM. Collagen-binding proteins in age-dependent changes in renal collagen turnover: microarray analysis of mRNA expression. Physiol Genomics 44: 576 -586, 2012. First published March 27, 2012 doi:10.1152/physiolgenomics.00186.2011.-Aging is associated with progressive structural and functional deterioration of the kidney. Among the morphological changes associated with renal aging is an accumulation of extracellular matrix (ECM) in the glomeruli and tubuloinsterstitium, which may ultimately lead to the development of renal fibrosis. The mechanisms governing the regulation of ECM metabolism during renal aging are only incompletely defined. We present data from a genome-wide mRNA expression study on renal tissue from 90 wk old male Wistar rats and 10 wk old controls using Illumina BeadArray cDNA microarray. Regulation of candidate gene products was verified by real-time PCR. Morphological changes were evaluated by routine histological methods. Activated fibroblasts were identified by their expression of alpha-smooth muscle actin and collagen I. Morphological analysis demonstrated an expansion of the tubulointerstitial compartment with increased amounts of fibrous collagen but no overt glomerular or tubular damage in the aged rats. Activated fibroblasts were readily detectable in the adventitial layer of large renal vessels in controls and were not found in the old animals. In agreement with this finding, gene expression analysis revealed significant downregulation of collagen I mRNA along with numerous other ECM components. Concomitantly, collagen-stabilizing proteins were induced, whereas matrix metalloproteinase 9, an enzyme involved in collagen breakdown, was reduced. In conclusion, our results suggest that ECM expansion during renal aging results from an augmented stabilization in conjunction with a reduced breakdown of collagen fibers. Collagen stabilizing proteins may be essential for the control of renal ECM turnover and the pathogenesis of kidney fibrosis.aging; kidney; extracellular matrix; rat STEADY GAINS IN LIFE EXPECTANCY have resulted in a progressive rise in the average age of the population of industrialized countries and have rendered the very old the fastest growing age group in the US, Japan, and Europe. Aging is associated with a raised all-cause morbidity and mortality and subsequently, an increased utilization of health care services. Among the organs particularly affected by the aging process is the kidney. A recent study found that glomerular filtration rate decreases by an average of 1 ml/1.73 m 2

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