Apoptosis and myofibroblast expression in human glomerular disease: a possible link with transforming growth factor-beta-1.
OBJECTIVE
The pathophysiological pathways involved in the pathogenesis and evolution of renal fibrosis, have not been fully elucidated. Transforming growth factor-beta(1) (TGF-beta(1)) is involved in the development of renal scarring. Apoptosis is responsible for intrinsic cell deletion observed in end-stage kidney disease. Myofibroblasts are involved in the development of renal fibrosis. This study investigates whether there is a potential relationship between apoptosis, myofibroblast infiltration and TGF-beta(1) expression in the kidney of patients with glomerulonephritis (GN).


METHODS
Forty patients with various types of GN were included in the study. Myofibroblasts and TGF-beta(1) positive cells were detected in kidney biopsies by immunohistochemistry, while apoptotic cells were detected by the in situ end labelling of fragmented DNA.


RESULTS
Myofibroblasts were identified in the glomeruli of some patients with severe mesangioproliferative GN and glomerulosclerosis but a more intensive myofibroblast expression was found in the renal interstitium. TGF-beta(1) was expressed in the cytoplasm of tubular epithelial cells, in the renal interstitium and in the glomeruli of patients with GN. Apoptotic cells were mainly detected in the tubules and interstitium and were present in areas with intense myofibroblast infiltration. Positive correlations were observed between the intensity of myofibroblast expression in the interstitium and apoptosis in the tubulointerstitial area (r = 0.521, p < 0.01) as well as TGF-beta(1) expression (r = 0.462, p < 0.05) and degree of renal impairment (r = 0.430, p < 0.05).


CONCLUSIONS
These observations suggest that myofibroblast infiltration and apoptosis along with TGF-beta(1) expression are associated with the development of interstitial fibrosis in patients with glomerular disease.
Goumenos
Dimitrios S
DS
Department of Internal Medicine-Nephrology, University Hospital of Patras, GR-26500 Patras, Greece. dgoumenos@med.upatras.gr
Tsamandas
Athanassios C
AC
El Nahas
A Meguid
AM
Thomas
Graham
G
Tsakas
Sotiris
S
Sotsiou
Florentia
F
Bonikos
Dionysis S
DS
Vlachojannis
John G
JG
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D000199:Actins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1