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HMGB1, TGF-β and NF-κB are associated with chronic allograft nephropathy
Shi-Qi Zhao1, Zhen-Zhen Xue1, Ling-Zhang Wang1
1Emergency Intensive Care Unit, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
Insights
High mobility group protein B1 (HMGB1), transforming growth factor-β1 (TGF-β1), and nuclear factor-κB (NF-κB) are significantly elevated in chronic allograft nephropathy (CAN). Their increased expression correlates with CAN severity and may drive renal interstitial fibrosis.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Chronic allograft nephropathy (CAN) is a major cause of kidney transplant failure.
- The molecular mechanisms underlying CAN progression, particularly the role of specific proteins, require further elucidation.
Purpose of the Study:
- To investigate the association between high mobility group protein B1 (HMGB1), transforming growth factor-β1 (TGF-β1), and nuclear factor-κB (NF-κB) in patients with CAN.
- To determine the clinical significance and expression levels of HMGB1, TGF-β1, and NF-κB in renal tissues of CAN patients.
Main Methods:
- Immunohistochemical staining to assess protein expression in renal tissues.
- Western blot analysis to quantify protein expression levels.
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to measure mRNA expression of HMGB1, TGF-β1, and NF-κB.
Main Results:
- HMGB1, TGF-β1, and NF-κB showed markedly positive expression in CAN renal tissues, increasing with CAN pathological grade (I, II, III).
- Expression levels of HMGB1, TGF-β1, and NF-κB were significantly higher in CAN patients compared to controls and correlated positively with CAN grade.
- A positive association was found among HMGB1, TGF-β1, and NF-κB expression, including their mRNA levels.
Conclusions:
- Abnormal expression of HMGB1, TGF-β1, and NF-κB is a significant manifestation of CAN.
- These proteins and their mRNA expression are closely associated with CAN pathological progression and may form a signaling pathway inducing renal interstitial fibrosis.
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.
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