Review
Biochemistry & Molecular Biology
Sung-Min Park, Tae-Il Kang, Jae-Seon So
Summary: XBP1s is an active transcription factor that plays a critical role in regulating UPR target genes to reduce ER stress. It also controls the transcription of genes involved in lipid and glucose metabolism, as well as immune responses. Understanding the target genes and transcriptional regulatory mechanisms of XBP1s will aid in developing new therapeutic targets for various diseases.
Article
Multidisciplinary Sciences
Aparajita Madhavan, Bernard P. Kok, Bibiana Rius, Julia M. D. Grandjean, Adekunle Alabi, Verena Albert, Ara Sukiasyan, Evan T. Powers, Andrea Galmozzi, Enrique Saez, R. Luke Wiseman
Summary: Signaling through the IRE1 arm of the unfolded protein response has both protective and harmful effects in obesity. A selective pharmacological activator of IRE1/XBP1s signaling can stimulate adaptive remodeling in the liver and pancreas, and mitigate obesity-linked metabolic dysfunction. The activator improves systemic glucose metabolism, liver insulin action, and enhances pancreatic function.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Wei-Bin Shen, Bingbing Wang, Ruofan Yao, Katherine R. Goetzinger, Sheng Wu, Haijun Gao, Peixin Yang
Summary: Maternal obesity is associated with adverse obstetrical outcomes and increased risk of congenital heart defects in fetuses. This study examines the activation of endoplasmic reticulum stress pathways in obese placenta.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Roberta Gonnella, Maria Saveria Gilardini Montani, Luisa Guttieri, Maria Anele Romeo, Roberta Santarelli, Mara Cirone
Summary: This study demonstrates the crucial role of the IRE1α/XBP1 axis in the survival of PEL cells, with minor influence from PERK and ATF6, and the ability of the IRE1α/XBP1 axis to induce the release of IL-6, IL-10, and VEGF. Additionally, IRE1α/XBP1 inhibition reduces STAT3 phosphorylation and induces pro-survival autophagy in PEL cells, suggesting that targeting this axis may be a promising strategy against PEL cells.
Article
Immunology
Margaud Iovino, Megan Colonval, Chloe Wilkin, Laurent L'homme, Cedric Lassence, Manon Campas, Olivier Peulen, Pascal de Tullio, Jacques Piette, Sylvie Legrand-Poels
Summary: In obesity, adipose tissue macrophages with pro-inflammatory polarization are important in chronic inflammation and Type 2 diabetes. Saturated fatty acids drive this polarization. In this study, the researchers investigated the immune and metabolic changes in human macrophages treated with saturated fatty acids. They found that glycolysis was upregulated in these macrophages and depended on HIF-1a activation, and that IRE1a played a key role in HIF-1a-mediated glycolysis upregulation through XBP1s-independent mechanism.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Kunpeng Qin, Hao Tang, Yi Ren, Di Yang, Yetian Li, Wei Huang, Yunfeng Wu, Zongsheng Yin
Summary: This study found that melatonin can inhibit chondrocyte apoptosis by promoting SIRT1 expression, and delay the progression of osteoarthritis in a mouse model.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jiangwei Xiao, Jingwen Huang, Xiaoting Jian, Han Wang, Haiqiang Lan, Zhaohong Liao, Ruicai Gu, Jijie Hu, Hua Liao
Summary: Endoplasmic reticulum stress and the unfolded protein response play a role in muscle pathology. The IRE1 alpha arm of the unfolded protein response affects the immunological properties of muscle fibers by inhibiting p38 MAPK activation under inflammatory conditions. This study examined the expression of TGF-beta and TGF-beta receptor II, as well as the activation of the unfolded protein response, in damaged muscle and regenerating myofibers. The findings suggest that TGF-beta signaling regulates muscle cell inflammation through the unfolded protein response-IRE1 alpha-p38 MAPK pathway.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2023)
Article
Oncology
Nancy T. Chee, Candace H. Carriere, Zachary Miller, Scott Welford, Shaun P. Brothers
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and difficult to treat cancer characterized by high levels of chronic hypoxia. The study reveals a previously unknown function of ATF4, a master regulator of the unfolded protein response pathway, in chronic hypoxia. ATF4 decreases HIF2 alpha mRNA and increases HIF1 alpha mRNA, leading to decreased cell migration but increased colony formation and cell viability in both chronic and acute hypoxia.
Article
Virology
Eduardo Alvarez-Rivera, Madeline Rodriguez-Valentin, Nawal M. Boukli
Summary: ADF cofilin-1 is a crucial component of the cytoskeleton and is involved in HIV-1 infection. The study found that Coriolus versicolor bioactive extract polysaccharide peptide (PSP) can inhibit HIV-1 replication and identified PKR and IRE1a as key regulators in cofilin-1 phosphorylation and viral restriction.
Article
Biochemistry & Molecular Biology
Rossella Benedetti, Andrea Arena, Maria Anele Romeo, Maria Saveria Gilardini Montani, Roberta Gonnella, Roberta Santarelli, Pankaj Trivedi, Mara Cirone
Summary: This study found that inhibiting the IRE1 alpha/XBP1 axis had a stronger cytotoxic effect on Burkitt lymphoma (BL) cells, correlated with c-Myc downregulation. In addition, inhibition of IRE1 alpha/XBP1 also downregulated BRCA-1 and RAD51 expression, and enhanced the cytotoxicity of PARP inhibitor against BL cells and Primary Effusion Lymphoma (PEL). These findings suggest a new therapeutic opportunity for treating aggressive B-cell lymphomas by combining inhibition of UPR sensors and molecules involved in DNA damage response (DDR).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Gaelle Mawambo, Malika Oubaha, Yusuke Ichiyama, Guillaume Blot, Sergio Crespo-Garcia, Agnieszka Dejda, Francois Binet, Roberto Diaz-Marin, Christina Sawchyn, Mikhail Sergeev, Rachel Juneau, Randal J. Kaufman, El Bachir Affar, Frederick A. Mallette, Ariel M. Wilson, Przemyslaw Sapieha
Summary: Cellular adaptation to low oxygen tension and metabolic stress in injured tissues is crucial for the proper functioning of inflammatory cells. In this study, we show that the inositol-requiring enzyme 1 alpha (IRE1 alpha/XBP1) axis is required for the initiation of HIF1 alpha-dependent cytokine production in innate immune cells. Knockout of either HIF1 alpha or IRE1 alpha improves vascular phenotypes in a model of retinal pathological angiogenesis driven by sterile inflammation. Thus, ER stress pathways, in partnership with HIF1 alpha, may co-regulate immune adaptation to low oxygen.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Oncology
Adriana Martinez-Turtos, Rachel Paul, Manuel Grima-Reyes, Hussein Issaoui, Adrien Krug, Rana Mhaidly, Jozef P. Bossowski, Johanna Chiche, Sandrine Marchetti, Els Verhoeyen, Eric Chevet, Jean-Ehrland Ricci
Summary: Overexpression and/or activation of IRE1 alpha in tumor cells can limit tumor growth, induce apoptosis in tumor cells, and enhance tumor immunosurveillance.
Article
Biochemistry & Molecular Biology
Yingxin Zhao, Dianhua Qiao, Melissa Skibba, Allan R. Brasier
Summary: RSV infection induces N-glycosylation and ECM secretion through the ULK pathway, which is closely associated with the IRE1 alpha-XBP1 branch. This finding expands our understanding of the role of the IRE1 alpha-XBP1 pathway in regulating structural remodeling of the epithelial basement membrane in RSV infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kosala N. Amarasinghe, Diana Pelizzari-Raymundo, Antonio Carlesso, Eric Chevet, Leif A. Eriksson, Sayyed Jalil Mahdizadeh
Summary: This study presents a detailed in silico screening targeting the dimer interface at the IRE1 RNase region, and identifies four compounds that can bind to and distort IRE1 RNase cavity. The compounds show significant inhibition of IRE1 phosphorylation and RNase activity, as demonstrated in cellular and in vitro assays. This study reveals a new and unique mode of action to target and block the IRE1-mediated UPR signaling.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Oncology
Sana Abbasi, Helia Rivand, Fatemeh Eshaghi, Mohammad Amin Moosavi, Saeid Amanpour, Michael F. Mcdermott, Marveh Rahmati
Summary: This study aimed to sensitize colorectal cancer cells to chemotherapy by targeting the IRE1a/XBP1 pathway. The results showed that the IRE1a inhibitor 4 mu 8C inhibited CRC cell growth and enhanced the cytotoxicity of 5-FU. In vivo experiments demonstrated that 4 mu 8C inhibited tumor growth and significantly enhanced drug responses when combined with 5-FU.
Article
Immunology
Ning Ma, Xiaoling Liu, Chen Xing, Xiaoqian Wang, Yinxiang Wei, Gencheng Han, Guojiang Chen, Chunmei Hou, Beifen Shen, Yan Li, He Xiao, Renxi Wang
CLINICAL IMMUNOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Xiaoqian Wang, Yinxiang Wei, Xiaoling Liu, Chen Xing, Gencheng Han, Guojiang Chen, Chunmei Hou, Ivy M. Dambuza, Beifen Shen, Yan Li, He Xiao, Renxi Wang
MOLECULAR IMMUNOLOGY
(2015)
Article
Cell Biology
Xiuduan Xu, Hongli Wang, Shasha Liu, Chen Xing, Yang Liu, Aodengqimuge, Wei Zhou, Xiaoyan Yuan, Yongfu Ma, Meiru Hu, Yongliang Hu, Shuxian Zou, Ye Gu, Shuangqing Peng, Shengtao Yuan, Weiping Li, Yuanfang Ma, Lun Song
Article
Oncology
Chen Xing, Gaizhi Zhu, He Xiao, Ying Fang, Xiaoling Liu, Gencheng Han, Guojiang Chen, Chunmei Hou, Beifen Shen, Yan Li, Ning Ma, Renxi Wang
Article
Immunology
Yinxiang Wei, Fanghui Zhang, Yu Zhang, Xiaoqian Wang, Chen Xing, Jing Guo, Hui Zhang, Zhimin Suo, Yan Li, Jianli Wang, Renxi Wang, Zhijian Cai
CELLULAR & MOLECULAR IMMUNOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Yongliang Hu, Rui Jin, Ming Gao, Huan Xu, Shuxian Zou, Xiaoguang Li, Chen Xing, Qiyu Wang, Hongli Wang, Jiannan Feng, Meiru Hu, Lun Song
Article
Multidisciplinary Sciences
Xiuduan Xu, Aodeng Qimuge, Hongli Wang, Chen Xing, Ye Gu, Shasha Liu, Huan Xu, Meiru Hu, Lun Song
SCIENTIFIC REPORTS
(2017)
Article
Oncology
B. Zhai, C. Hou, R. Xu, Y. Fang, N. Ma, C. Xing, X. Wang, H. Xiao, G. Chen, G. Han, R. Wang
CLINICAL & TRANSLATIONAL ONCOLOGY
(2020)
Article
Immunology
Youdi He, Ruonan Xu, Bing Zhai, Ying Fang, Chunmei Hou, Chen Xing, He Xiao, Guojiang Chen, Xiaoqian Wang, Ning Ma, Gencheng Han, Renxi Wang
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Ying Fang, Youdi He, Bing Zhai, Chunmei Hou, Ruonan Xu, Chen Xing, Xiaoqian Wang, Ning Ma, Gencheng Han, Renxi Wang
Summary: The deficiency of Itch in B cells promotes antigen-induced B-cell activation and antibody production, while not significantly affecting spleen and lymph node sizes, antibody levels, and antibody gene mutations. Itch deficiency accelerates antigen-induced cytokine production by controlling proteins with translation initiation factor activity.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Chen Xing, Xin Huang, Yifan Zhang, Chongchong Zhang, Wei Wang, Lin Wu, Mengnan Ding, Min Zhang, Lun Song
FRONTIERS IN GENETICS
(2020)
Article
Neurosciences
Chen Xing, Yanzhao Zhou, Huan Xu, Mengnan Ding, Yifan Zhang, Min Zhang, Meiru Hu, Xin Huang, Lun Song
Summary: Sleep loss can lead to mood disorders such as anxiety and depression, but the underlying mechanisms are not fully understood. Research showed that sleep deprivation for 3 days induced anxiety and depression-like behaviors in rats, along with alterations in the circadian oscillations of clock genes and neuroinflammation.
NEUROSCIENCE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Wei Wang, Yifan Zhang, Mengnan Ding, Xin Huang, Min Zhang, Yu Gu, Lin Wu, Chongchong Zhang, Chunfeng Lu, Beifen Shen, Chen Xing, Lun Song
Summary: Sleep disturbance can induce abnormal increase in OTC levels in the liver, but levels can return to normal after recovery sleep. The expression of OTC shows circadian oscillation, which is closely related to the expression of RORα.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Meeting Abstract
Clinical Neurology
Chen Xing, Ye Gu, Xin Huang, Meiru Hu, Lun Song