Transforming growth factor-β1 and tumor growth factor-β-inducible gene-H3 in nonrenal transplant cyclosporine nephropathy

Cyclosporine nephropathy (CyAN) is a major limiting factor in the otherwise successful widespread use of cyclosporine in solid organ transplant. Transforming growth factor-β1 (TGF-β1) has been implicated as an important fibrogenic cytokine in the development of this disease. TGF-β-inducible gene-H3 (βig-H3) is a TGF-β1- induced gene product, which acts as a marker for biologically active TGF-β1. This study reports TGF-β1 gene expression and βig-H3 tissue distribution in non-renal allograft CyAN. Renal tissue from nine patients who had developed CyAN after successful heart or heart-lung transplantation and from four kidneys removed for tumour were analyzed for TGF-β1 gene expression βig-H3 protein with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. TGF-β1 gene expression was increased in CyAN compared to nephrectomy (P<0.0001). βig-H3 protein expression was identified in distal convoluted tubular epithelium and parietal glomerular epithelium in CyAN, and not in nephrectomy samples. Expression of TGF-β1 mRNA was significantly higher in renal tissue from patients not receiving angiotensin converting enzyme inhibitor (ACEI) therapy for hypertension (P<0.05). These findings support the hypothesis that TGF-β1 is an important cytokine in the development of CyAN, independent of its role in chronic rejection in renal allografts.