title: Protein overload activates proximal tubular cells to release vasoactive and inflammatory mediators.
abstract: Chronic renal diseases with highly enhanced glomerular permeability to proteins are accompanied by tubulointerstitial inflammation and scarring and progression to renal failure. As a consequence of increased glomerular permeability, proteins filtered through the glomerular capillary in excessive amount have intrinsic renal toxicity at least partially linked to their accumulation in the proximal tubular cell cytoplasm during the process of reabsorption along the nephron. Experimental evidence is available showing that protein overload per se activates proximal tubular epithelial cells in culture to upregulate genes encoding for endothelin, chemokines and cytokines. These vasoactive and inflammatory substances, formed in excessive quantities by the tubular cells, are released mainly into the basolateral compartment, a pattern of secretion that in the kidney would favor recruitment and activation of inflammatory cells into the renal interstitium and fibrogenic reaction leading to renal scarring.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Zoja
authors.forename: A
authors.initials: A
authors.lastname: Benigni
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000042:Absorption; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D011506:Proteins / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D016232:Endothelins; D011506:Proteins