Specific accumulation of exogenous fibronectin in experimental glomerulosclerosis.
The prognosis of patients showing glomerulosclerosis as a complication of an immunologically mediated kidney disease is poor. To improve the diagnosis and treatment of these patients, it is important to understand the processes involved in the development of glomerulosclerosis. In this study, we investigated the molecular composition of experimental end-stage glomerular sclerotic lesions and their pathogenesis in chronic graft-versus-host disease (GvHD) in the mouse and chronic serum sickness in the rat. Accumulation studies were performed to determine the degree of specific trapping of constituents from the circulation. Two different models were investigated to determine whether differences in disease initiation resulted in different compositions of the glomerulosclerotic lesions. In both models, glomerulosclerosis was preceded by expansion of the mesangial matrix and thickening of the glomerular basement membrane (GBM). The end-stage sclerotic lesions consisted mainly of fibronectin, which appeared to displace the other extracellular matrix (ECM) components peripherally in the mesangial matrix and GBM. The abundance of fibronectin in the lesions was not reflected in the mRNA levels for this component. Indeed, antibodies directed against the cellular form of fibronectin did not stain positive in the end-stage lesions. These findings, together with accumulation studies, suggest that specific accumulation rather than de novo synthesis of fibronectin plays a major role in the development of experimental glomerulosclerosis, which appears to be independent of the pathway of induction.
Bergijk
E C
EC
Department of Pathology, University of Leiden, The Netherlands.
Baelde
H J
HJ
De Heer
E
E
Killen
P D
PD
Bruijn
J A
JA
D000818:Animals; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology; D006086:Graft vs Host Disease / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016253:Microscopy, Immunoelectron; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012713:Serum Sickness / Q000378:metabolism* / Q000473:pathology
D005353:Fibronectins; D012333:RNA, Messenger