Growth factors and apoptosis-related protein expression in human crescentic nephritis.
BACKGROUND
Crescentic nephritis is a renal disease that rapidly progresses toward renal failure unless aggressive immunosuppressive treatment is administered. Gene-directed apoptosis is involved in the resolution of renal injury or its progression toward scarring. In the present study, the expressions of growth factors, myofibroblasts [alpha-SMA(+) cells], and apoptosis-related proteins, were estimated to identify their contribution to the organization of crescents and to the clinical course of the disease.


METHODS
The extent of immunostaining for EGF, IGF-1, TGF-beta1, alpha-SMA(+) cells, as well as bax and bcl-2 proteins was estimated in cellular, fibrocellular, and fibrotic crescents of 17 kidney biopsy specimens from patients with crescentic nephritis, and correlated with the clinical course of the disease.


RESULTS
Growth factors, apoptosis-related proteins, and myofibroblasts were identified within crescents, glomeruli, and tubulointerstitial area. EGF and bax protein were mainly identified in cellular crescents (>50%) whereas TGF-beta1, myofibroblasts, and bcl-2 protein were observed in fibrocellular crescents (>50%). The expression of all parameters was significantly reduced in fibrotic crescents. The presence of glomeruli with a ruptured Bowman capsule and an increased serum creatinine level at diagnosis were associated with an unfavorable clinical course with no response to immunosuppressive therapy (P<0.05 and P<0.02, respectively).


CONCLUSIONS
Growth factors and the apoptotic process are involved in the organization of cellular to fibrotic crescents resulting in irreversible damage and an unfavorable clinical outcome. Identifying different patterns among growth factors and apoptosis-related proteins during the organization of crescents suggests an interplay between growth factors and the apoptotic process in the development of crescentic nephritis.
Goumenos
Dimitrios S
DS
Department of Internal Medicine-Nephrology University Hospital, Patras, Greece. dgoumenos@med.upatras.gr
Kalliakmani
Pantelitsa
P
Tsakas
Sotiris
S
Papachristou
Evangelos
E
Vlachojannis
John G
JG
D000293:Adolescent; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; D036341:Intercellular Signaling Peptides and Proteins