The decreased expression of electron transfer flavoprotein β is associated with tubular cell apoptosis in diabetic nephropathy

Wang,Hua; Zhang,Haojun; Chen,Xiaohong; Zhao,Tingting; Kong,Qin; Yan,Meihua; Zhang,Bingxuan; Sun,Sifan; Lan,Hui-Yao; Li,Ning; Li,Ping

doi:10.3892/ijmm.2016.2533

The decreased expression of electron transfer flavoprotein β is associated with tubular cell apoptosis in diabetic nephropathy

Authors:
- Hua Wang
- Haojun Zhang
- Xiaohong Chen
- Tingting Zhao
- Qin Kong
- Meihua Yan
- Bingxuan Zhang
- Sifan Sun
- Hui-Yao Lan
- Ning Li
- Ping Li
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Affiliations: Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, P.R. China, Department of Nephrology, Chinese Medicine Hospital of Shaanxi, Xi'an, Shaanxi, P.R. China, Li Ka Shing Institute of Health Sciences and Department of Medicine and Therapeutics, and Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong SAR, P.R. China, Institute of Basic Medical Science, Peking Union Medical College, Beijing, P.R. China
Published online on: March 18, 2016 https://doi.org/10.3892/ijmm.2016.2533
Pages: 1290-1298
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tubular injury is closely correlated with the development of progressive diabetic nephropathy (DN), particularly in cases of type 2 diabetes. The apoptosis of tubular cells has been recognized as a major cause of tubular atrophy, followed by tubulointerstitial fibrosis. Electron transfer flavoprotein β (ETFβ) is known as an important electron acceptor in energy metabolism, but its role in DN was not fully understood. In the present study, we examined the expression pattern of ETFβ using diabetic kidney samples and further investigated ETFβ involvement in tubular epithelial cell (TEC) apoptosis. Human renal biopsy specimens from patients with DN as well as a spontaneous rat model of diabetes using Otsuka Long-Evans Tokushima fatty (OLETF) rats, were employed in order to examine the expression of ETFβ and cell apoptosis in kidneys during the development of DN (for the rats, at 36 and 56 weeks of age respectively). Moreover, ETFβ siRNA was used to investigate the role of ETFβ in the apoptosis of renal tubular cells. Our present results showed that the expression of ETFβ in the kidneys was progressively decreased both in patients with DN and OLETF rats, which coincided with progressive renal injury and TEC apoptosis. In addition, the in vitro study demonstrated that knockdown of ETFβ caused apoptosis in tubular cells, as proven by the increased expression of pro‑apoptotic proteins and TUNEL assay. Therefore, the findings of our present study suggest that ETFβ plays an important role in renal tubular cell apoptosis during the progression of DN.

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