IMR Press / FBL / Volume 14 / Issue 5 / DOI: 10.2741/3343

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

The role of chemokines in progressive renal disease
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1 Mario Negri Institute for Pharmacological Research, via Gavazzeni 11, 24125 Bergamo, Italy
2 Division of Nephrology and Dialysis Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Largo Barozzi 1, 24128 Bergamo, Italy
Front. Biosci. (Landmark Ed) 2009, 14(5), 1815–1822;
Published: 1 January 2009

Tubulointerstitial damage followed by scarring and progressive loss of renal function is common to many forms of chronic proteinuric nephropathies. The severity of tubulointerstitial injury and in particular interstitial macrophage infiltration strongly correlate with the risk of renal failure. Proteins filtered through the glomerular capillary in excessive amount activate proximal tubular cells to upregulate chemokines mainly via activation of NF-kappaB-dependent pathway. Chemokines secreted toward the basolateral compartment of tubular epithelial cells incite local recruitment of mononuclear cells, that in turn interact with resident renal cells and extracellular matrix to create a proinflammatory microenvironment that amplifies tubulointerstitial inflammation and promotes renal scarring. The association between proteinuria and interstitial accumulation of inflammatory cells via activation of transcription factors and overexpression of chemokines has been established both experimentally and in human proteinuric nephropathies. Blocking leukocyte recruitment by interfering with transcription factor activity or chemokines and their receptors is envisioned as a strategy to retard kidney disease progression.

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