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).
Conclusion: 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.