HMGB1, TGF-β and NF-κB are associated with chronic allograft nephropathy.

Abstract

The present study aimed to investigate the association between high mobility group protein B1 (HMGB1), transforming growth factor-β1 (TGF-β1), nuclear factor-κB (NF-κB) and chronic allograft nephropathy (CAN) and to identify the clinical significance of HMGB1, TGF-β1, NF-κB on patients with CAN. Between September 2012 and November 2014, 27 patients with CAN diagnosed by biopsy were enrolled in the present study and a further 30 patients that underwent nephrectomy following trauma were selected as the control group. Immunohistochemical staining with HMGB1, TGF-β1 and NF-κB expression in the renal tissues, and western blot analysis were used to measure the relative expression of HMGB1, TGF-β1 and NF-κB. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to estimate the relative expression of HMGB1, TGF-β1 and NF-κB mRNA. Statistical analysis was used to calculate the association between HMGB1, TGF-β1 and NF-κB expression and CAN grade. Immunohistochemical staining demonstrated that HMGB1, TGF-β1 and NF-κB had markedly positive expression rates in renal tubular epithelial cell cytoplasm and membranes in CAN renal tissues, and the positive rates of HMGB1, TGF-β1 and NF-κB increased with the aggravation of CAN pathological grade (I, II and III). The results of western blot analysis indicated that the expression levels of HMGB1, TGF-β1 and NF-κB were significantly higher in the CAN group, compared with the normal group (P<0.05), and the expression levels increased with the progression of CAN grade. A positive association among HMGB1, TGF-β1 and NF-κB expression was identified. RT-qPCR analysis demonstrated that the expression of HMGB1, TGF-β1 and NF-κB mRNA in the CAN group was significantly higher than in the normal group (P<0.05), and the relative expression level of HMGB1, TGF-β1 and NF-κB mRNA not only increased with the aggravation of CAN grade, but was also positively associated with the expression of HMGB1, TGF-β1 and NF-κB, respectively. The abnormal expression of HMGB1, TGF-β1 and NF-κB is therefore, an important manifestation of CAN and the expression of HMGB1, TGF-β1 and NF-κB mRNA in the renal tissues are significantly associated with CAN pathological progression. HMGB1, TGF-β1 and NF-κB may form a signaling pathway that leads to the occurrence of CAN, which induces renal interstitial fibrosis.