Expression and significance of TGF-beta1/Smad signaling pathway in children with IgA nephropathy.
BACKGROUND
IgA nephropathy (IgAN) exhibits an indolent but slowly progressive course, and about 30% of children with IgAN are found to deteriorate to end-stage renal failure characterized by overaccumulation of extracellular matrix, diffuse glomerular sclerosis, and tubulointerstitial fibrosis. The TGF-beta/Smad signaling pathway plays an important role in glomerulosclerosis and tubulointerstitial fibrosis. The present study aimed to elucidate the significance of expressions of TGF-beta1, phosphorylated Smad3 (p-Smad3), Smad7 and fibronectin (FN) in the renal tissue of children with IgAN.


METHODS
Forty-six children with IgAN were divided into 3 groups according to their clinical features: isolated hematuria group (IH group, 8 patients), hematuria and proteinuria group (HP group, 24), and nephritic syndrome group (NS group, 14). Patients were also divided into three groups according to their pathologic grade: grade I+II (22 patients), grade III (12) and grade IV (12) groups. Five normal renal specimens were used as the control group. The expression of TGF-beta1, p-Smad3, Smad7 and FN in renal biopsy specimens was detected by two-step PowerVision. The degrees of renal tubular injury and interstitial fibrosis were scored according to the Katafuchi semi-quantitative criteria.


RESULTS
The expression of TGF-beta1, p-Smad3, Smad7 and FN in children with IgAN was significantly higher than that in the control group (in glomeruli: P<0.05, P<0.01, P<0.05 and P<0.01, respectively; in tubulointerstitium: P<0.05, P<0.05, P<0.01 and P<0.05, respectively) and the highest expression levels were found in the NS and grade IV groups (P<0.05, P<0.01). The expression levels of the four proteins were not only positvely correlated with each other, but also with the grade of renal tubular injury and renal interstitial fibrosis (P<0.05).


CONCLUSIONS
The TGF-beta1/Smad signaling pathway plays an important role in the progress of glomerular sclerosis, renal tubular injury and interstitial fibrosis in children with IgAN.
Wu
Wei
W
Department of Pediatrics, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
Jiang
Xiao-Yun
XY
Zhang
Qiao-Ling
QL
Mo
Ying
Y
Sun
Liang-Zhong
LZ
Chen
Shu-Mei
SM
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D051785:Smad Proteins / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D005353:Fibronectins; D007070:Immunoglobulin A; C497790:SMAD3 protein, human; C497806:SMAD7 protein, human; D051785:Smad Proteins; D051900:Smad3 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1
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