Renal cell apoptosis and proliferation may be linked to nuclear factor-kappaB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis.
The mechanism of renal cell apoptosis involves transcriptional activation of the inducible nitric oxide synthase (iNOS) gene by nuclear factor (NF)-kappaB. The role of apoptosis in mediating tubulointerstitial injury in human lupus nephritis (LN) remains unclear. We examined the relationship between alterations in NF-kappaB activation and iNOS expression levels and the degree of apoptosis in both glomerular and tubulointerstitial compartments of subjects with LN. Studies were done in renal biopsies from 49 patients with LN and 10 normal kidney tissues. Apoptotic and proliferating cells were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and staining with anti-proliferating cell nuclear antigen antibody, respectively. Nuclear factor-kappaB and iNOS expression was examined by Southwestern histochemistry and immunohistochemistry, respectively. Glomerular cell apoptosis and proliferation increased concomitantly in LN. Glomerular apoptosis correlated with the activity index, the degree of proliferation, and the level of glomerular overexpression of iNOS and activated NF-kappaB in LN. Tubular cell apoptosis correlated with the activity and chronicity indices, the degree of tubular atrophy, and decline in renal function at the time of biopsy. Tubular expression of iNOS and activated NF-kappaB correlated with tubular cell proliferation in LN. Nuclear factor-kappaB activation accompanied overexpression of iNOS in both glomerular and tubulointerstitium compartments in LN. Apoptosis of renal cells associated with NF-kappaB activation and iNOS overexpression may play an important role in mediating chronic renal injury, especially tubulointerstitial lesions that may manifest clinically as progressive renal insufficiency.
Zheng
Ling
L
Department of Pathology, National University of Singapore, Singapore.
Sinniah
Raja
R
Hsu
Stephen I-Hong
SI
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005920:Glomerular Mesangium / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000201:enzymology / Q000378:metabolism; D008181:Lupus Nephritis / Q000201:enzymology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012189:Retrospective Studies; D015533:Transcriptional Activation
D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D052247:Nitric Oxide Synthase Type II