Transcription factor Sp1 expression is upregulated in human glomerulonephritis: correlation with pSmad2/3 and p300 expression and renal injury.
BACKGROUND
Sp1 is a ubiquitous transcription factor that mediates the fibrogenic factor transforming growth factor beta (TGF-beta) signals through cooperation with Smad proteins. The transcriptional coactivator p300 is also suggested to play a role in Smad signal transduction.


METHODS
We investigated the immunohistochemical expression of Sp1 as well as the expression of pSmad2/3 and the coactivator p300 in 157 renal biopsy specimens from patients with various types of glomerulonephritis (GN). Correlations between immunohistochemical, clinical, and histologic parameters were performed.


RESULTS
Sp1 exhibited an increased glomerular and proximal tubular expression in all forms of GN compared to controls. The proximal tubular expression of Sp1 was significantly increased in proliferative GNs (p = 0.025), whereas in secondary GNs, there was a significant increase in the molecule's glomerular expression (p = 0.008). Sp1 correlated positively with pSmad2/3 and p300 expression in proximal tubules (r = 0.241, p = 0.018 and r = 0.244, p = 0.014, respectively), while in proliferative GNs, its expression correlated positively with pSmad2/3 expression in glomeruli (r = 0.32, p = 0.028). Sp1 glomerular and proximal tubular immunostaining correlated positively with serum creatinine levels (r = 0.265, p = 0.02 and r = 0.306, p = 0.006, respectively), while its proximal tubular expression showed a similar correlation with interstitial fibrosis (r = 0.213, p = 0.025). Sp1 was constantly detected in hyperplastic lesions and cellular crescents (each 100%), and very often in micro adhesions (94%) and segmentally or globally sclerotic areas (each 83%).


CONCLUSIONS
This study documents the upregulation of Sp1 expression in glomeruli and proximal tubules of GN specimens. Our findings suggest a possible cooperation of Sp1 with pSmad2/3 and p300 in mediating renal injury as well as a possible role for this molecule in the pathogenesis and the progression of human GN.
Kassimatis
Theodoros Ioannis
TI
Department of Nephrology, Evangelismos General Hospital, Athens, Greece. tkassimatis@yahoo.gr
Nomikos
Alexandros
A
Giannopoulou
Ioanna
I
Lymperopoulos
Anastasios
A
Moutzouris
Dimitrios-Anestis
DA
Varakis
Ioannis
I
Nakopoulou
Lydia
L
D000328:Adult; D001706:Biopsy; D016009:Chi-Square Distribution; D050881:E1A-Associated p300 Protein; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D051900:Smad3 Protein; D016329:Sp1 Transcription Factor; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human