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Expression of decay accelerating factor mRNA and complement C3 mRNA in human diseased kidney
1Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Background:
Decay accelerating factor (DAF), a product of mesangial cells in vitro, is expressed on the surface of cells and is a candidate for the focal suppression of complement activation. It is not clear at present whether the levels of expression of DAF and intrarenal C3 synthesis correlate with the level of tissue injury.
Methods:
Immunohistochemistry for DAF and C3 and nonradioactive in situ hybridization with digoxigenin-labeled oligonucleotide probe for DAF and C3 mRNA were performed in 22 tissue samples of kidneys from patients with IgA nephropathy (IgAN), 6 with membranous nephropathy (MN), 6 with lupus nephritis (LN), and five normal kidneys.
Results:
In the normal kidney, DAF was confined to the juxtaglomerular apparatus and little or no C3 was detected; however, a few glomerular cells were positive for DAF mRNA but no C3 mRNA positive cells were detected. In diseased kidneys, DAF and C3 as well as their mRNAs were detected in mesangial cells, tubular cells and infiltrating cells. Glomerular epithelial cells and Bowman's capsule cells contained little or no DAF and C3 but were positive for their mRNAs. The mean percentages of mesangial cells positive for DAF and C3 mRNAs were 49.3 +/- 11.5% and 50.7 +/- 10.3% in IgAN, and 17.0 +/- 6.3% and 19.4 +/- 9.0% in MN, respectively. The percentage of mesangial cells positive for DAF and C3 mRNAs among intraglomerular cells correlated positively with the degree of mesangial proliferation and glomerular sclerosis in IgAN. In contrast, in LN the percentage of glomerular cells positive for DAF mRNA correlated negatively with the degree of glomerular injury, while the percentage of cells positive for C3 mRNA did not change with the progression of the disease. The ratio of C3 mRNA/DAF mRNA of glomerular cells correlated with the degree of glomerular injury in both IgAN and LN. In the tubulointerstitium, the percentage of cells expressing mRNA, and C3 mRNA/DAF mRNA radio correlated with the degree of tubular atrophy and interstitial broadening in both IgAN and LN.
Conclusions:
We conclude that DAF and C3 mRNAs are synthesized in human diseased kidneys, and that a balance between locally synthesized DAF and C3 may be important in the progression of glomerulonephritis.
Insights
Decay accelerating factor (DAF) and C3 mRNA are synthesized in diseased human kidneys, suggesting their local balance is crucial for glomerulonephritis progression. This study investigates their correlation with tissue injury in various nephropathies.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Decay accelerating factor (DAF) is expressed on cell surfaces and may suppress complement activation.
- The correlation between DAF and C3 synthesis levels and intrarenal tissue injury remains unclear.
Purpose of the Study:
- To investigate the expression and localization of DAF and C3 and their mRNAs in normal and diseased human kidneys.
- To determine if DAF and C3 synthesis correlates with the severity of kidney injury in IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN).
Main Methods:
- Immunohistochemistry and in situ hybridization were used to detect DAF, C3, and their respective mRNAs in kidney tissue samples.
- Samples included 22 IgAN, 6 MN, 6 LN, and 5 normal kidneys.
Main Results:
- In normal kidneys, DAF was localized to the juxtaglomerular apparatus, with minimal C3 detected. DAF mRNA was present in some glomerular cells, but C3 mRNA was absent.
- In diseased kidneys, DAF and C3, along with their mRNAs, were found in mesangial, tubular, and infiltrating cells. Glomerular epithelial and Bowman's capsule cells showed mRNA but little protein.
- The ratio of C3 mRNA to DAF mRNA in glomerular cells correlated with glomerular injury in IgAN and LN. In the tubulointerstitium, mRNA expression and the C3/DAF mRNA ratio correlated with tubular atrophy and interstitial broadening.
Conclusions:
- DAF and C3 mRNAs are synthesized within diseased human kidneys.
- The balance between locally synthesized DAF and C3 appears to play a significant role in the progression of glomerulonephritis.