Increased renal expression of cytokines and growth factors induced by DOCA-NaCl treatment in Heymann nephritis.
DOCA-NaCl treatment causes hypertension, accelerates development of proteinuria, and leads to glomerulosclerosis in rats with autoimmune Heymann nephritis. To study the mechanisms of kidney injury induced by renal haemodynamic load in chronic nephritis, we studied by immunohistochemistry the local expression of various cytokines, growth factors and adhesion molecules in the kidneys of Heymann nephritic rats with or without DOCA-NaCl-induced hypertension. The DOCA-NaCl-nephritis group developed hypertension and marked renal enlargement as compared with the nephritis group, the DOCA-NaCl group, and the controls. Albuminuria appeared earlier and was heavier in the DOCA-NaCl-nephritis group compared with the nephritic rats without DOCA-NaCl. Expression of IL-6, TNF-alpha, GM-CSF, b-FGF, NGF, TGF-beta, and ICAM-1 was enhanced in the kidneys of the DOCA-NaCl-nephritis group as compared with other groups, localized mainly in the glomerular mesangium (IL-6, GM-CSF, TGF-beta), glomerular and peritubular endothelium (ICAM-1), and collecting ducts (TNF-alpha, b-FGF, NGF, TGF-beta), possibly associated with the observed tubulointerstitial mononuclear cellular infiltration. Thus in autoimmune Heymann nephritis, DOCA-NaCl treatment causes hypertension and increased renal mass together with upregulation of local cytokine and growth factor production, which may further aggravate hypertension and accelerate progression of renal damage.
Tikkanen
I
I
Minerva Institute for Medical Research, Helsinki University Central Hospital, Finland.
Uhlenius
N
N
Tikkanen
T
T
Miettinen
A
A
Törnroth
T
T
Fyhrquist
F
F
Holthöfer
H
H
D000818:Animals; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000009:adverse effects*; D018450:Disease Progression; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006133:Growth Substances / Q000378:metabolism*; D007150:Immunohistochemistry; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D006133:Growth Substances; D003900:Desoxycorticosterone