Expression of decay accelerating factor mRNA and complement C3 mRNA in human diseased kidney

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.