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Browsing by Author "Liu, Yu"
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Item Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury(Springer Nature, 2019-09-12) Tang, Chengyuan; Han, Hailong; Liu, Zhiwen; Liu, Yuxue; Yin, Lijun; Cai, Juan; He, Liyu; Liu, Yu; Chen, Guochun; Zhang, Zhuohua; Yin, Xiao-Ming; Dong, Zheng; Pathology and Laboratory Medicine, School of MedicineAcute kidney injury (AKI) is a syndrome of abrupt loss of renal functions. The underlying pathological mechanisms of AKI remain largely unknown. BCL2-interacting protein 3 (BNIP3) has dual functions of regulating cell death and mitophagy, but its pathophysiological role in AKI remains unclear. Here, we demonstrated an increase of BNIP3 expression in cultured renal proximal tubular epithelial cells following oxygen-glucose deprivation-reperfusion (OGD-R) and in renal tubules after renal ischemia-reperfusion (IR)-induced injury in mice. Functionally, silencing Bnip3 by specific short hairpin RNAs in cultured renal tubular cells reduced OGD-R-induced mitophagy, and potentiated OGD-R-induced cell death. In vivo, Bnip3 knockout worsened renal IR injury, as manifested by more severe renal dysfunction and tissue injury. We further showed that Bnip3 knockout reduced mitophagy, which resulted in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and enhanced cell death and inflammatory response in kidneys following renal IR. Taken together, these findings suggest that BNIP3-mediated mitophagy has a critical role in mitochondrial quality control and tubular cell survival during AKI.Item Asparagine bioavailability regulates the translation of MYC oncogene(Springer Nature, 2022) Srivastava, Sankalp; Jiang, Jie; Misra, Jagannath; Seim, Gretchen; Staschke, Kirk A.; Zhong, Minghua; Zhou, Leonardo; Liu, Yu; Chen, Chong; Davé, Utpal; Kapur, Reuben; Batra, Sandeep; Zhang, Chi; Zhou, Jiehao; Fan, Jing; Wek, Ronald C.; Zhang, Ji; Pediatrics, School of MedicineAmino acid restriction has recently emerged as a compelling strategy to inhibit tumor growth. Recent work suggests that amino acids can regulate cellular signaling in addition to their role as biosynthetic substrates. Using lymphoid cancer cells as a model, we found that asparagine depletion acutely reduces the expression of c-MYC protein without changing its mRNA expression. Furthermore, asparagine depletion inhibits the translation of MYC mRNA without altering the rate of MYC protein degradation. Of interest, the inhibitory effect on MYC mRNA translation during asparagine depletion is not due to the activation of the general controlled nonderepressible 2 (GCN2) pathway and is not a consequence of the inhibition of global protein synthesis. In addition, both the 5' and 3' untranslated regions (UTRs) of MYC mRNA are not required for this inhibitory effect. Finally, using a MYC-driven mouse B cell lymphoma model, we found that shRNA inhibition of asparagine synthetase (ASNS) or pharmacological inhibition of asparagine production can significantly reduce the MYC protein expression and tumor growth when environmental asparagine becomes limiting. Since MYC is a critical oncogene, our results uncover a molecular connection between MYC mRNA translation and asparagine bioavailability and shed light on a potential to target MYC oncogene post-transcriptionally through asparagine restriction.Item Effects of biomechanical forces on signaling in the cortical collecting duct (CCD)(American Physiological Society (APS), 2014-07-15) Carrisoza-Gaytan, Rolando; Liu, Yu; Flores, Daniel; Else, Cindy; Lee, Heon Goo; Rhodes, George; Sandoval, Ruben M.; Kleyman, Thomas R.; Lee, Francis Young-In; Molitoris, Bruce; Satlin, Lisa M.; Rohatgi, Rajeev; Department of Medicine, IU School of MedicineAn increase in tubular fluid flow rate (TFF) stimulates Na reabsorption and K secretion in the cortical collecting duct (CCD) and subjects cells therein to biomechanical forces including fluid shear stress (FSS) and circumferential stretch (CS). Intracellular MAPK and extracellular autocrine/paracrine PGE2 signaling regulate cation transport in the CCD and, at least in other systems, are affected by biomechanical forces. We hypothesized that FSS and CS differentially affect MAPK signaling and PGE2 release to modulate cation transport in the CCD. To validate that CS is a physiological force in vivo, we applied the intravital microscopic approach to rodent kidneys in vivo to show that saline or furosemide injection led to a 46.5 ± 2.0 or 170 ± 32% increase, respectively, in distal tubular diameter. Next, murine CCD (mpkCCD) cells were grown on glass or silicone coated with collagen type IV and subjected to 0 or 0.4 dyne/cm2 of FSS or 10% CS, respectively, forces chosen based on prior biomechanical modeling of ex vivo microperfused CCDs. Cells exposed to FSS expressed an approximately twofold greater abundance of phospho(p)-ERK and p-p38 vs. static cells, while CS did not alter p-p38 and p-ERK expression compared with unstretched controls. FSS induced whereas CS reduced PGE2 release by ∼40%. In conclusion, FSS and CS differentially affect ERK and p38 activation and PGE2 release in a cell culture model of the CD. We speculate that TFF differentially regulates biomechanical signaling and, in turn, cation transport in the CCD.Item Exploring inbound tourists experience in Beijing, China: an online deductive approach(Emerald, 2019) Liu, Yu; Liu-Lastres, Bingjie; Wang, Qiuju; Fu, Yao-Yi; Tourism, Conventions, and Event Management, School of Physical Education and Tourism ManagementPurpose Beijing is becoming one of the top global destinations but the number of international tourists to the city has been declining recently. By analyzing inbound tourists experience in Beijing and identifying the relationship between the destination attributes and satisfaction, the purpose of this paper is to provide important insights into city tourism research and city destination development. Design/methodology/approach This study used an online deductive approach and collected 1,254 reviews on TripAdvisor referencing major attractions in Beijing. This study used the Leximancer software to analyze the content of the reviews and to identify the underlying relationships. Findings The results showed that international tourists’ experience in Beijing can be reflected via five aspects: attractions, city, transportation, service and people. The results further indicated that the major concern of international tourists visiting Beijing related to the service quality on site. Originality/value This study explored inbound tourists experience in Beijing using an online deductive approach. Practical implications were provided with respect to improving international tourists experience in Beijing and enhancing their satisfaction and revisiting intentions.Item KMT2D-NOTCH Mediates Coronary Abnormalities in Hypoplastic Left Heart Syndrome(American Heart Association, 2022) Yu, Zhiyun; Zhou, Xin; Liu, Ziyi; Pastrana-Gomez, Victor; Liu, Yu; Guo, Minzhe; Tian, Lei; Nelson, Timothy J.; Wang, Nian; Mital, Seema; Chitayat, David; Wu, Joseph C.; Rabinovitch, Marlene; Wu, Sean M.; Snyder, Michael P.; Miao, Yifei; Gu, Mingxia; Radiology and Imaging Sciences, School of MedicineItem PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury(Taylor & Francis, 2018) Tang, Chengyuan; Han, Hailong; Yan, Mingjuan; Zhu, Shiyao; Liu, Jing; Liu, Zhiwen; He, Liyu; Tan, Jieqiong; Liu, Yu; Liu, Hong; Sun, Lin; Duan, Shaobin; Peng, Youming; Liu, Fuyou; Yin, Xiao-Ming; Zhang, Zhuohua; Dong, Zheng; Pathology and Laboratory Medicine, School of MedicineDamaged or dysfunctional mitochondria are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Therefore, timely removal of these organelles is critical to cellular homeostasis and viability. Mitophagy is the mechanism of selective degradation of mitochondria via autophagy. The significance of mitophagy in kidney diseases, including ischemic acute kidney injury (AKI), has yet to be established, and the involved pathway of mitophagy remains poorly understood. Here, we show that mitophagy is induced in renal proximal tubular cells in both in vitro and in vivo models of ischemic AKI. Mitophagy under these conditions is abrogated by Pink1 and Park2 deficiency, supporting a critical role of the PINK1-PARK2 pathway in tubular cell mitophagy. Moreover, ischemic AKI is aggravated in pink1 andpark2 single- as well as double-knockout mice. Mechanistically, Pink1 and Park2 deficiency enhances mitochondrial damage, reactive oxygen species production, and inflammatory response. Taken together, these results indicate that PINK1-PARK2-mediated mitophagy plays an important role in mitochondrial quality control, tubular cell survival, and renal function during AKI.