title: Increased Tbx1 expression may play a role via TGFβ-Smad2/3 signaling pathway in acute kidney injury induced by gentamicin.
abstract: T-box 1 (Tbx1) gene is closely involved in embryonic kidney development. To explore the role of Tbx1 in acute kidney injury (AKI) and the underlying mechanism, we detected the expression of Tbx1 and components of transforming growth factor-beta (TGF-β) signaling pathways including TGF-β, phosphorylated Smad2/3 (p-Smad2/3) and phosphorylated Smad1/5/8 (p-Smad1/5/8) in kidney tissues derived from a rat model for AKI induced by gentamicin (GM). Apoptosis of renal cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), along with the expression of two essential genes involved in apoptosis, caspase-3 and Bcl-2. Correlation between Tbx1 expression and the number of TUNEL-positive cells was analyzed by a Spearman test. Expression of TGF-β, p-Smad2/3 and p-Smad1/5/8 in Tbx1-knockdown NRK cells was also analyzed by real-time RT-PCR and Western blotting. Markedly increased Tbx1 expression was found in the injured kidney tissues, which has activated the TGFβ-Smad2/3 pathway whilst suppressed Smad1/5/8 expression. Conversely, decreased TGF-β and p-Smad2/3 levels, and elevated p-Smad1/5/8 levels were detected in Tbx1-knockdown NRK cells. More apoptotic cells were detected in the injured kidneys, which has well correlated with the expression of Tbx1. Expression of caspase-3 was markedly increased, while Bcl-2 was decreased in the injured kidney tissues. Above findings suggested that activation of Tbx1 is involved in AKI through the TGFβ-Smad2/3 pathway. Tbx1 expression may therefore serve as a marker for AKI, and Tbx1-blocking therapies may provide an option for treating GM-induced nephropathy.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of China Medical University Shenyang 110001, China.
authors.forename: Hongkun
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Sino-Dutch Biomedical and Information Engineering School, Northeastern University Shenyang 110003, China ; Institute of Medical Genetics, School of Life Science, Joint Key Laboratory for Bio-resource Research and Utilization of Sichuan and Chongqing, Sichuan University Chengdu 610064, China.
authors.forename: Jesse
authors.initials: J
authors.lastname: Li-Ling
authors.affiliation: Department of Medical Genetics, China Medical University Shenyang 110001, China.
authors.forename: Guangrong
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of China Medical University Shenyang 110001, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of China Medical University Shenyang 110001, China.
authors.forename: Yaoguo
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Medical Genetics, China Medical University Shenyang 110001, China.
authors.forename: Kailai
authors.initials: K
authors.lastname: Sun
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005839:Gentamicins / Q000009:adverse effects; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005839:Gentamicins; D019253:Proto-Oncogene Proteins c-bcl-2; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D020825:T-Box Domain Proteins; C000595281:Tbx1 protein, rat; D016212:Transforming Growth Factor beta; D053148:Caspase 3
keywords: Acute kidney injury; Smad1/5/8; Smad2/3; TGF-β; Tbx1; gentamicin