ECM homeostasis in renal diseases: a genomic approach

Abstract

Chronic renal disease is in general histologically accompanied by a vast amount of scar tissue, ie glomerulosclerosis and interstitial fibrosis. Scarring results from excessive accumulation of extracellular matrix (ECM) components, a process driven by a plethora of cytokines and growth factors. Studies in experimental renal disease which target these regulators using gene therapy limit or prevent the development of scarring. This review focuses specifically on the role of transforming growth factor-beta, platelet-derived growth factor, connective tissue growth factor, hepatocyte growth factor, and epidermal growth factor. The results obtained in animal models hold promise for molecular intervention strategies in human renal disease. Microarray technology allows large-scale gene expression profiling in kidney tissue to identify common molecular pathways in a step towards discovery of new drug targets. Molecular techniques are expected to be used for diagnostic and prognostic purposes in nephrological practice to supplement renal biopsy. Several studies already show that molecular techniques might be of use in routine diagnostic practice. Improvement of diagnosis and prediction of outcome in renal patients might lead to more efficient and earlier therapeutic intervention.

Decreased Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinase in the Kidneys of Hereditary Nephrotic (ICGN) Mice

“…nents, and influence cell morphology and functions, such as cell migration, proliferation, apoptosis and so on. The production and degradation of the ECM are accurately regulated in quantity and quality in healthy mammals, but under pathological conditions this balance is upset, and the homeostatic regulation of cell morphology and function can not be maintained [1,14]. Consequently, abnormal regulation of ECM metabolism causes the progression of fibrosis.…”

“…A balance between the production and degradation of the ECM is maintained to achieve tissue homeostasis, but is disrupted under pathological conditions [1]. Hyper-production and/or hypo-degradation of the ECM can cause fibrosis in many organs, ex.…”

“…The quality and quantity of extracellular matrix (ECM) components are tightly regulated in normal tissue, cell migration, proliferation, apoptotic cell death and so on. A balance between the production and degradation of the ECM is maintained to achieve tissue homeostasis, but is disrupted under pathological conditions [1]. Hyper-production and/or hypo-degradation of the ECM can cause fibrosis in many organs, ex.…”

Human Nephrosclerosis Triggers a Hypoxia-Related Glomerulopathy

“…1 The glomerular gene expression data demonstrated significant overrepresentation of GO terms of two biological processes potentially involved in hypoxia-related kidney damage: angiogenesis (eg, the GO terms "angiogenesis" Because a corresponding GO term does not exist, we used a literature-based list of genes potentially involved in renal fibrosis. [35][36][37][38] Of 84 fibrosis-related genes derived from the literature, 83 were represented on the HG-U133A array. Of these, 73 genes showed mRNA expression above the cutoff in the expression array analysis of the glomeruli from NSC biopsy specimens.…”

Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization

“…Efficiencies (E) were calculated from the given slopes in the Light Cycler software using dilutions of total RNA prepared from U87 cell line and shown to be 1.82 for PLEKHB1 assay, 1.81 for DNER assay, 1.96 for DEC1 assay, 1.87 for SPOCK1 and TIMP3 assays, and 1.91 for OPN assay. The QPCR conditions for FN and 18S RNA levels have been previously described (Eikmans et al, 2003;Rocchi et al, 2004). The relative expression ratio (R) of the target mRNA and reference rRNA (18S) was calculated using QPCR efficiencies (E) and the crossing point (Cp) deviation of a tumor sample versus the U87 RNA cell line used as control as previously described (Pfaffl, 2001).…”