title: The accumulation of extracellular matrix in the kidney: consequences on cellular function.
abstract: The mechanisms involved in the progression of chronic renal disease (CRD) have not been completely clarified. A role for hyperfiltration and increased intraglomerular pressure was proposed about twenty years ago, and experimental and clinical evidence supports, at least partially, this hypothesis. Moreover, a lot of experimental data point to the importance of different autacoids, including prostanoids, endothelial vasoactive factors, reactive oxygen species, cytokines and growth factors, in the genesis of the changes that characterize CRD. However, alternative mechanisms of progression may be involved such as the presence of abnormal extracellular matrix (ECM) proteins in kidney structures. By modifying the phenotype of renal cells, they may constitute a key factor in disease progression. Experimental studies support this hypothesis. Human mesangial cells cultured on collagen I (COLI) synthesize increased amounts of TGFss1 compared with cells cultured on collagen IV (COLIV). As a consequence of this increased TGFBeta1 synthesis, they also produce more collagens and fibronectin. Human umbilical vein endothelial cells cultured on COLI show a different pattern of endothelial vasoactive factor synthesis, compared with those on COLIV: they synthesize more endothelin-1 and less nitric oxide. Integrins and integrin-linked kinase (ILK) play a significant role in the genesis of these changes. Although an extrapolation of these data to human diseases can not be performed, they point to alternative mechanisms of chronic renal damage progression or renal dysfunction in kidney diseases. They also point to potential therapeutic targets such as integrins and ILK.
authors: Research Unit and Nephrology Section, Hospital Principe de Asturias and Instituto Reina Sofia, Alcala de Henares, Madrid, Spain.
authors: María Piedad
authors: MP
authors: Ruiz-Torres
authors: Susana
authors: S
authors: López-Ongil
authors: Mercedes
authors: M
authors: Griera
authors: Maria Luisa
authors: ML
authors: Díez-Marqués
authors: Manuel
authors: M
authors: Rodríguez-Puyol
authors: Diego
authors: D
authors: Rodríguez-Puyol
mesh_terms: D000818:Animals; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology
chemical_list: D016326:Extracellular Matrix Proteins