Immunolocalization of acidic fibroblast growth factor and receptors in the tubulointerstitial compartment of chronically rejected human renal allografts.
Tubular damage and loss associated with interstitial inflammation and fibrosis may be the most important determinants in chronic renal allograft rejection. To elucidate potential pathophysiologic mechanisms associated with tubulointerstitial lesions, we examined the expression of a fibrogenic cytokine, acidic fibroblast growth factor (FGF-1) and its high-affinity receptors, in both relevant renal transplant controls (n=5) and tissue from patients (n=19) who underwent nephrectomy after graft loss, secondary to chronic rejection. In situ hybridization and immunohistochemical analyses demonstrated minimal expression of FGF-1 mRNA and protein in the tubulointerstitial compartment of the normal human kidney. In contrast, tubulointerstitial lesions in kidney allografts experiencing chronic rejection demonstrated the exaggerated appearance of both FGF-1 protein and mRNA in resident inflammatory and tubular epithelial cells. Patterns of staining were consistent throughout tubular compartments and did not appear to be localized to any particular region. The tubulointerstitium in kidneys with findings of chronic rejection also exhibited increased immunodetection of proliferating cell nuclear antigen in the tubular epithelium, inflammatory cell infiltrate, and neovascular structures. The enhanced appearance of FGF-1 and readily detectable fibroblast growth factor receptors suggests that this polypeptide mitogen may serve as an important mediator of growth and repair responses, associated with development of angiogenesis and tubulointerstitial lesions during chronic rejection of human renal allografts.
Kerby
J D
JD
Department of Surgery, School of Medicine, University of Alabama at Birmingham, 35294, USA.
Luo
K L
KL
Ding
Q
Q
Tagouri
Y
Y
Herrera
G A
GA
Diethelm
A G
AG
Thompson
J A
JA
D015415:Biomarkers / Q000032:analysis; D002908:Chronic Disease; D016220:Fibroblast Growth Factor 1 / Q000032:analysis* / Q000235:genetics; D006084:Graft Rejection; D006801:Humans; D017403:In Situ Hybridization; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000737:chemistry*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis* / Q000235:genetics; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D014841:von Willebrand Factor; D016220:Fibroblast Growth Factor 1