title: The decreased expression of electron transfer flavoprotein β is associated with tubular cell apoptosis in diabetic nephropathy.
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.
authors.affiliation: Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, P.R. China.
authors.forename: Haojun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Chinese Medicine Hospital of Shaanxi, Xi'an, Shaanxi, P.R. China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, P.R. China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Yan
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, P.R. China.
authors.forename: Bingxuan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Sifan
authors.initials: S
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Hui-Yao
authors.initials: HY
authors.lastname: Lan
authors.affiliation: Institute of Basic Medical Science, Peking Union Medical College, Beijing, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015415:Biomarkers; D001786:Blood Glucose; D001835:Body Weight; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D044927:Electron-Transferring Flavoproteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D051381:Rats
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D044927:Electron-Transferring Flavoproteins; D008055:Lipids