Cytomegalovirus enhance expression of growth factors during the development of chronic allograft nephropathy in rats.
Cytomegalovirus (CMV) accelerates chronic rejection (CRX) in a model of rat kidney allograft. In this model, the expressions of transforming growth factor beta 1 (TGF-beta), platelet-derived growth factor (PDGF)-AA, PDGF-BB and connective tissue growth factor (CTGF) were investigated with and without CMV. Transplantations were performed under immunosuppression. One group of animals was infected with CMV and the other was left uninfected. The grafts were harvested on days 3-60 after transplantation. Growth factor proteins were demonstrated by immunohistochemistry, and mRNAs by in situ hybridization. A significantly more intense and earlier endothelial TGF-beta (2.4 +/- 0.8 vs. 1.0 +/- 0.0; P < 0.05) and PDGF-AA (1.8 +/- 0.4 vs. 1.0 +/- 0.0; P < 0.05) expressions, confirmed by mRNA hybridization, occurred in the CMV group compared with the noninfected group. PDGF-BB appeared in a few inflammatory cells only. In addition CTGF appeared earlier and has more intense in the CMV group (2.5 +/- 0.6 vs. 1.2 +/- 0.5) and the number of CTGF mRNA-positive fibroblasts (57 +/- 9 vs. 3 +/- 4; P < 0.05) was significantly higher. Thus, CMV enhanced expression of TGF-beta1, PDGF-AA and CTGF during the development of CRX.
Inkinen
Kaija
K
Department of Virology, Helsinki University Central Hospital and Helsinki University, Helsinki, Finland. kaija.inkinen@hus.fi
Soots
Anu
A
Krogerus
Leena
L
Loginov
Raisa
R
Bruggeman
Cathrien
C
Lautenschlager
Irmeli
I
D000818:Animals; D002908:Chronic Disease; D055513:Connective Tissue Growth Factor; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D005355:Fibrosis; D006084:Graft Rejection / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000032:analysis* / Q000235:genetics; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics; D014184:Transplantation, Homologous
C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor