کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3840017 | 1597937 | 2016 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of Src and forkhead box O1 signaling by induced pluripotent stem-cell therapy attenuates hyperoxia-augmented ventilator-induced diaphragm dysfunction
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کلمات کلیدی
MDAMuscle RING finger-1FOXO1poly (ADP-ribose) polymerase 1PARP1iPSC-CMIPSCsLC3MuRF-1ROS - ROSubiquitin-proteasome pathway - ubiquitin-پروتئازوم مسیرAcute lung injury - آسیب ریه حادVentilator-induced lung injury - آسیب ریه ناشی از تهویهAli - اماUpP - بالاMechanical ventilation - تهویه مکانیکیlight chain 3 - زنجیره سبک 3Induced pluripotent stem cells - سلول های بنیادی پرتوان القاییmalondialdehyde - مالون دی آلدهیدVILI - ویلیReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mechanical ventilation (MV) with hyperoxia is required for providing life support to patients with acute lung injury (ALI). However, MV may cause diaphragm weakness through muscle injury and atrophy, an effect termed ventilator-induced diaphragm dysfunction (VIDD). Src protein tyrosine kinase and class O of forkhead box 1 (FoxO1) mediate acute inflammatory responses and muscle protein degradation induced by oxidative stress. Induced pluripotent stem cells (iPSCs) have been reported to improve hyperoxia-augmented ALI; however, the mechanisms regulating the interactions among VIDD, hyperoxia, and iPSCs are unclear. In this study, we hypothesized that iPSC therapy can ameliorate hyperoxia-augmented VIDD by suppressing the Src-FoxO1 pathway. Male C57BL/6 mice, either wild-type or Src-deficient, aged between 6 and 8Â weeks were exposed to MV (6 or 10Â mL/kg) with or without hyperoxia for 2-8Â h after the administration of 5 Ã 107 cells/kg Oct4/Sox2/Parp1 mouse iPSCs or iPSC-derived conditioned medium (iPSC-CM). Nonventilated mice were used as controls. MV during hyperoxia aggravated VIDD, as demonstrated by the increases in Src activation, FoxO1 dephosphorylation, malondialdehyde, caspase-3, atrogin-1 and muscle ring finger-1 production, microtubule-associated protein light chain 3-II, disorganized myofibrils, disrupted mitochondria, autophagy, and myonuclear apoptosis; however, MV with hyperoxia reduced mitochondrial cytochrome C, diaphragm muscle fiber size, and contractility (PÂ <Â 0.05). Hyperoxia-exacerbated VIDD was attenuated in Src-deficient mice and by iPSCs and iPSC-CM (PÂ <Â 0.05). Our data indicate that iPSC therapy attenuates MV-induced diaphragmatic injury that occurs during hyperoxia-augmented VIDD by inhibiting the Src-FoxO1 signaling pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 173, July 2016, Pages 131-147.e1
Journal: Translational Research - Volume 173, July 2016, Pages 131-147.e1
نویسندگان
Li-Fu Li, Yuh-Lih Chang, Ning-Hung Chen, Chien-Ying Wang, Gwo-Jyh Chang, Meng-Chih Lin, Chih-Hao Chang, Chung-Chi Huang, Jen-Hua Chuang, Yi-Pin Yang, Shih-Hwa Chiou, Yung-Yang Liu,