Disruption of glomerular cell-cell and cell-matrix interactions in hydrocarbon nephropathy.
Environmental chemicals play an etiological role in greater than 50% of idiopathic glomerular diseases. The present studies were conducted to define mechanisms of renal cell-specific hydrocarbon injury. Female rats were given 10 mg/kg benzo(a)pyrene (BaP) once a week for 16 wk. Progressive elevations in total urinary protein, protein/creatinine ratios, and microalbuminuria were observed in rats treated with BaP for up to 16 wk. The nephropathic response involved early reductions in mesangial cell numbers and fibronectin levels by 8 wk, coupled to transient increases in podocyte cellularity. Changes in podocyte numbers subsided by 16 wk and correlated with rebound increases in mesangial cell numbers and fibronectin levels, along with increased alpha-smooth muscle actin and Cu/Zn superoxide dismutase and fusion of podocyte foot processes. In culture, mesangial cells were more sensitive than podocytes to hydrocarbon injury and expressed higher levels of inducible aryl hydrocarbon hydroxylase activity. Naïve mesangial cells exerted a strong inhibitory influence on podocyte proliferation under both direct and indirect coculture conditions, and this response involved a mesangial cell-derived matrix that selectively inhibited podocyte proliferation. These findings indicate that hydrocarbon nephropathy in rats involves disruption of glomerular cell-cell and cell-matrix interactions mediated by deposition of a mesangial cell-derived growth-inhibitory matrix that regulates podocyte proliferation.
Department of Physiology and Pharmacology, Texas A&M University College of Veterinary Medicine, College Station, USA.
Adrian
A
Nanez
Napoleon F
NF
Alejandro
M Hadi
MH
Falahatpisheh
J Kevin
JK
Kerzee
John B
JB
Roths
Kenneth S
KS
Ramos
D000818:Animals; D001564:Benzo(a)pyrene; D002450:Cell Communication / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000166:cytology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System