Increased expression of insulin-like growth factors in progressive glomerulonephritis of the MRL/lpr mouse.
Glomerulonephritis is an important complication of systemic lupus erythematosus (SLE). The tissue distribution and exact role of the insulin-like growth factors (IGFs) in the development of lupus nephritis in the MRL/lpr mouse model have not been established. The present study was undertaken to evaluate the changes over time in mRNA and peptide expression of IGF-I and IGFBP-2 in the MRL/lpr mouse. Using in situ hybridization and immunocytochemistry techniques, the expression of IGF-I and IGFBP-2 in MRL/lpr mouse was examined and compared to their congenic normal MRL-++ mouse counterparts from nine to 24 weeks of age. In the MRL-++ and MRL/lpr mouse kidneys, IGF-I and IGFBP-2 mRNA expression was limited to the cortical and medullary collecting ducts, while their immunoreactivity (IR) was localized to the cortical and medullary collecting ducts, loop of Henle, glomeruli and proximal tubules. Over time, and with progression of disease, the MRL/lpr mice displayed a significant increase in IGF-I IR and a modest increase in IGFBP-2 IR within the outer cortical glomeruli, which was associated with a significant increase in glomerulosclerosis and glomerular cell proliferation and with a significant decrease in renal function. In conclusion, this overexpression of IGF-I and IGFBP-2 within the glomeruli of the MRL/lpr mouse kidney supports their potential role in the alterations in renal function and morphology that accompany lupus nephritis.
Mohammed
J A
JA
Department of Pediatrics and Child Health Research Institute, University of Western Ontario, London, Ontario, Canada.
Mok
A Y P
AY
Parbtani
A
A
Matsell
D G
DG
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005919:Glomerular Filtration Rate / Q000502:physiology; D005921:Glomerulonephritis / Q000378:metabolism*; D007150:Immunohistochemistry; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D007672:Kidney Cortex / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009399:Nephrons / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D013002:Somatomedins / Q000096:biosynthesis*
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D013002:Somatomedins; D017526:Receptor, IGF Type 1