Review
Immunology
Xu Liu, Feng Lu, Xihang Chen
Summary: This review discusses the role of necroptotic DAMPs in tissue fibrosis and highlights the inflammatory responses induced by DAMPs in tissue ECM remodeling. By summarizing the existing literature, it provides a framework for future investigations into the relationship among necroptosis, DAMPs, and fibrosis, as well as a reference for later transformation into clinical treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jin Young Jeong, Ki Ryang Na, Jin Ah Shin, Kwang-Sun Suh, Jwa-Jin Kim, Kang Wook Lee, Dae Eun Choi
Summary: This study revealed that collecting duct-specific mitochondrial injury may exacerbate inflammation and fibrosis in chronic kidney disease, and could worsen renal injury induced by unilateral ureteral obstruction (UUO). Mitochondrial damage associated oxidative stress may play a role in worsening UUO-induced renal injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Sabira Mohammed, Nidheesh Thadathil, Ramasamy Selvarani, Evan H. Nicklas, Dawei Wang, Benjamin F. Miller, Arlan Richardson, Sathyaseelan S. Deepa
Summary: The study revealed an association between liver aging and increased necroptosis, leading to chronic inflammation and fibrosis in the aging liver.
Article
Toxicology
Huihui Tao, Hui Zhao, Deyong Ge, Jinjun Liao, Luocheng Shao, Aowei Mo, LeLin Hu, Keyi Xu, Jing Wu, Min Mu, Bin Li, Xinrong Tao, Jianhua Wang
Summary: The necroptotic signaling pathway of macrophages is significantly activated in the lungs of silicosis mouse models, promoting the progression of silicosis through enhancing lung inflammatory responses and fibrogenesis. Increased M1 macrophage infiltration and up-regulation of pro-inflammatory cytokines were observed in this study, along with the up-regulation of pro-fibrotic factors and fibrosis biomarkers, which were recovered by the specific inhibitor of RIP1 kinase-dependent necroptosis. These findings provide new insights for the treatment of silicosis.
TOXICOLOGY LETTERS
(2022)
Article
Chemistry, Medicinal
Yi Sun, Lijuan Xu, Hongming Shao, Danni Quan, Zixin Mo, Jue Wang, Wannian Zhang, Jianqiang Yu, Chunlin Zhuang, Ke Xu
Summary: The study found that RIPK1 plays an important role in inflammation and necroptosis, as well as in the pathogenesis of AD. The RIPK1 inhibitor SZM679 showed promising therapeutic effects in an AD mouse model, improving cognitive function, reducing neuronal loss, and decreasing Tau hyperphosphorylation, neuroinflammation, and RIPK1 phosphorylation levels.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Sarah Ali Abdelhameed Gouda, Basma Emad Aboulhoda, Omaima Mohammed Abdelwahed, Hend Abdallah, Laila Rashed, Rania Elsayed Hussein, Nivin Sharawy
Summary: The present study found that low-intensity pulsed ultrasound (LIPUS) can inhibit the pro-inflammatory response of M1 macrophages and promote the anti-inflammatory response of M2 macrophages in acute kidney injury. It also reverses gentamicin-induced renal damage by inhibiting necroptosis and reducing the expression of heat shock protein-70.
Article
Cell Biology
Junjun Luan, Jingqi Fu, Congcong Jiao, Xiangnan Hao, Zixuan Feng, Lingzi Zhu, Yixiao Zhang, Guangyu Zhou, Hongyu Li, Wei Yang, Peter S. T. Yuen, Jeffrey B. Kopp, Jingbo Pi, Hua Zhou
Summary: This study investigated the role of interleukin-18 (IL-18) in the progression from acute kidney injury (AKI) to chronic kidney disease (CKD). The results showed that IL-18 deficiency can attenuate renal tubular damage, necroptosis, cell transdifferentiation, and fibrosis, and this renoprotective effect may be mediated by reducing the switch from M1 to profibrotic M2 macrophages.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Jae-Hyung Park, Jaechan Leem, Sun-Jae Lee
Summary: Renal fibrosis, a common feature of chronic kidney disease, is a promising therapeutic target. This study found that carnosol (CS), a compound found in rosemary plants, improved renal function and reduced renal tubular injury and interstitial fibrosis in a murine model of unilateral ureteral obstruction (UUO). CS achieved this by suppressing oxidative stress, endoplasmic reticulum stress, apoptotic and necroptotic cell death, as well as cytokine production and immune cell infiltration in the kidneys.
Article
Biochemistry & Molecular Biology
Jun Wei, Min Li, Zhi Ye, Xinqian Hu, Xiaoyan He, Jia Wang, Gaofeng Chen, Chengyu Zou, Daichao Xu, Hongbing Zhang, Junying Yuan, Yunhong Zha
Summary: This study investigated the repurposing of primidone as a RIPK1 inhibitor in ALS patients. The results showed that primidone can inhibit RIPK1 and significantly reduce serum levels of RIPK1 and IL-8 in ALS patients. The serum levels of RIPK1 and IL-8 may serve as clinical biomarkers for RIPK1 activation in ALS patients.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Bing-feng Hu, Qian Gong, Shi-qing Chen, Lin Yue, Wen-xian Ma, Fang Wang, Xiao-wen Feng, Jia-nan Wang, Chao Li, Ming-ming Liu, Xue-fu Wang, Xiao-ming Meng, Jun Li, Jia-gen Wen
Summary: Necroptosis plays a role in gentamicin-induced acute kidney injury, and suppressing necroptosis could be a promising strategy for prevention.
Article
Physiology
Chuanming Xu, Yanting Chen, Nirupama Ramkumar, Chang-Jiang Zou, Curt D. Sigmund, Tianxin Yang
Summary: This study investigates the role of intrarenal RAAS in potassium homeostasis, specifically focusing on the action of renin in the collecting duct. The study found that mice with renal-specific deletion of renin had impaired potassium excretion and elevated plasma potassium levels when fed a high potassium diet. Additionally, the expression of intrarenal aldosterone and related proteins were also decreased.
Article
Biochemistry & Molecular Biology
Pedro L. R. Guedes, Carolina P. F. Carvalho, Adriana A. F. Carbonel, Manuel J. Simoes, Marcelo Y. Icimoto, Jair A. K. Aguiar, Maria Kouyoumdjian, Marcos L. Gazarini, Marcia R. Nagaoka
Summary: Chondroitin sulfate (CS) has been found to have therapeutic effects in an experimental model of bile duct ligation. CS reduces collagen content and increases liver parenchyma content, and can alter the hepatic collagen III/I ratio. Additionally, CS reduces cell death indicators and promotes regeneration. Therefore, CS has potential hepatoprotective action in fibrogenesis induced by bile duct ligation.
Review
Pharmacology & Pharmacy
Min Hao, Xin Han, Zhouhui Yao, Han Zhang, Mengting Zhao, Mengyun Peng, Kuilong Wang, Qiyuan Shan, Xianan Sang, Xin Wu, Lu Wang, Qiang Lv, Qiao Yang, Yini Bao, Haodan Kuang, Hongyan Zhang, Gang Cao
Summary: Fibrosis is a common response to chronic progressive diseases, characterized by excessive deposition of extracellular matrix. Different types of cell death are closely related to organ fibrosis, among which necroptosis is considered as a potential target to ameliorate fibrosis.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Fabian Bock, Bertha C. Elias, Xinyu Dong, Diptiben Parekh, Glenda Mernaugh, Olga M. Viquez, Anjana Hassan, Venkateswara Rao Amara, Jiageng Liu, Kyle L. Brown, Andrew S. Terker, Manuel Chiusa, Leslie S. Gewin, Agnes B. Fogo, Cord H. Brakebusch, Ambra Pozzi, Roy Zent
Summary: The study demonstrates that Rac1 is not essential for epithelial branching morphogenesis during kidney collecting duct development, but plays a crucial role in maintaining epithelial integrity, polarity, and function by Arp2/3-dependent cytoskeletal branching. This function of Rac1 involves restricting actomyosin activity. Despite a mild developmental phenotype in mice with selectively deleting Rac1 at the initiation of UB development, aging leads to disruption of epithelial integrity and function in the collecting duct, which is reversible with direct myosin II inhibition. Additionally, Rac1 controls lateral membrane height and overall epithelial morphology by restricting actomyosin and promoting CD epithelial integrity.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Environmental Sciences
Yue Wang, Shengchen Wang, Tong Xu, Wei Cui, Xu Shi, Shiwen Xu
Summary: This study investigated the types and mechanisms of damage caused by different diameters of polystyrene microplastics (PS-MPs) to mice bladder epithelial cells. The results showed that both diameters of PS-MPs led to necroptosis and inflammation in the bladder epithelium. 1-10 μm PS-MPs caused more severe necroptosis, while 50-100 μm PS-MPs led to a higher degree of inflammatory injury. Mechanistically, PS-MPs induced necroptosis and p-NF kappa B-mediated inflammation by triggering oxidative stress and excessive release of reactive oxygen species (ROS). Furthermore, N-Acetyl-L-cysteine (NAC) attenuated the toxic effects of PS-MPs on bladder epithelial cells.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Microbiology
Ying Shi, Lu Zhong, Yuting Li, Yanfang Chen, Shufen Feng, Min Wang, Yin Xia, Shaohui Tang
Summary: The study showed that Rgmb deficiency leads to dysbiosis of gut microbiota in mice, particularly a significant reduction in Prevotellaceae, which may render mice more susceptible to intestinal inflammation. This highlights RGMb as a potential novel target for reconstructing gut microbiota in the treatment of IBD.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Juan Huang, Yujie Pu, Hongsong Zhang, Liping Xie, Lei He, Cheng-Lin Zhang, Chak Kwong Cheng, Yingsong Huo, Song Wan, Shaoliang Chen, Yuhong Huang, Chi Wai Lau, Li Wang, Yin Xia, Yu Huang, Jiang-Yun Luo
Summary: The study indicates that blood flow plays a crucial role in vascular calcification, with calcification more likely to occur in branched areas. KLF2 inhibits vascular calcification by regulating endothelial BMP/SMAD1/5 signaling pathway.
CIRCULATION RESEARCH
(2021)
Article
Medicine, Research & Experimental
Rui Wang, Shi-Ting Wu, Xi Yang, Yude Qian, Jaesung P. Choi, Rui Gao, Siliang Song, Yixuan Wang, Tao Zhuang, Justin J. L. Wong, Yuzhen Zhang, Zhiming Han, Hua A. Lu, Stephen Alexander, Renjing Liu, Yin Xia, Xiangjian Zheng
Summary: The PDCD10-STK-ERM signaling pathway was identified as a potentially novel pathway for water balance control in the kidneys, by regulating vesicle trafficking and protein abundance of AQP2. Deficiency of Pdcd10 or Stk24/25 in mice led to decreased levels of Aqp2 protein in tubular epithelial cells, associated with impaired intracellular vesicle trafficking and increased expression of certain proteins. Treatment with Erlotinib normalized the expression level and membrane abundance of Aqp2 protein, partially rescuing the water reabsorption defect.
Article
Biochemistry & Molecular Biology
Congcong Wang, Kunying Hao, Lixia Dong, Jingnan Wang, Linchun Zhao, Lijun Xu, Yin Xia, Qing Jiang, Jinzhong Qin
Summary: This study using CRISPR/Cas9 genome editing demonstrated that deficiency of Lin54 or Lin52 components of the cell cycle regulatory MuvB complex in ESCs leads to G2/M arrest, loss of pluripotency, and spontaneous differentiation, with activation of mesoendodermal lineage-specifying genes. Furthermore, abnormalities in Lin54-null ESCs were partially rescued by ectopic coexpression of genes encoding G2/M proteins Cyclin B1 and Cdk1. These findings provide new insights into how the MuvB complex determines cell fate through regulation of the cell cycle machinery.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Urology & Nephrology
Api Chewcharat, Elizabeth A. Phipps, Khushboo Bhatia, Sahir Kalim, Andrew S. Allegretti, Meghan E. Sise, Teodor G. Paunescu, Rituvanthikaa Seethapathy, Sagar U. Nigwekar
Summary: The prevalence of olfactory dysfunction is higher in patients with chronic kidney disease (CKD), while there is no significant association between CKD and gustatory dysfunction. Decreased grip strength is associated with higher odds of olfactory dysfunction in CKD patients.
Article
Biochemistry & Molecular Biology
Yu Zhang, Yang Wang, Guoxun Zheng, Yang Liu, Jinhong Li, Huihui Huang, Chunhua Xu, Yelin Zeng, Xiaoyi Zhang, Jinzhong Qin, Chunsun Dai, Harald O. Hambrock, Ursula Hartmann, Bo Feng, Kingston Kinglun Mak, Youhua Liu, Hui-Yao Lan, Yu Huang, Zhi-Hua Zheng, Yin Xia
Summary: The study reveals that FSTL1 plays a promoting role in renal fibrosis by interacting with Wnt ligands and FZD receptors to activate the Wnt/β-catenin pathway. This finding is of great importance for a deeper understanding of the mechanism underlying kidney diseases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Otorhinolaryngology
Zara M. Patel, Eric H. Holbrook, Justin H. Turner, Nithin D. Adappa, Mark W. Albers, Aytug Altundag, Simone Appenzeller, Richard M. Costanzo, Ilona Croy, Greg E. Davis, Puya Dehgani-Mobaraki, Richard L. Doty, Valerie B. Duffy, Bradley J. Goldstein, David A. Gudis, Antje Haehner, Thomas S. Higgins, Claire Hopkins, Caroline Huart, Thomas Hummel, Kawinyarat Jitaroon, Robert C. Kern, Ashoke R. Khanwalkar, Masayoshi Kobayashi, Kenji Kondo, Andrew P. Lane, Matt Lechner, Donald A. Leopold, Joshua M. Levy, Michael J. Marmura, Lisha Mclelland, Takaki Miwa, Paul J. Moberg, Christian A. Mueller, Sagar U. Nigwekar, Erin K. O'Brien, Teodor G. Paunescu, Robert Pellegrino, Carl Philpott, Jayant M. Pinto, Evan R. Reiter, David R. Roalf, Nicholas R. Rowan, Rodney J. Schlosser, James Schwob, Allen M. Seiden, Timothy L. Smith, Zachary M. Soler, Leigh Sowerby, Bruce K. Tan, Andrew Thamboo, Bozena Wrobel, Carol H. Yan
Summary: This article reviews the literature on clinical olfaction, olfactory loss, and olfactory dysfunction over the past two decades and introduces the International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). Nearly 100 topics were thoroughly reviewed, providing important insights and clear guidance for the diagnosis and treatment of patients, while also highlighting gaps in our knowledge and evidence base.
INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
(2022)
Article
Cell & Tissue Engineering
Yaru Zhu, Lixia Dong, Congcong Wang, Kunying Hao, Jingnan Wang, Linchun Zhao, Lijun Xu, Yin Xia, Qing Jiang, Jinzhong Qin
Summary: Polycomb group proteins form PRC1 subcomplexes that play a crucial role in cell fate determination during embryonic development. Non-canonical PRC1 is essential for maintaining ESC pluripotency, and there is functional redundancy between non-canonical and canonical PRC1. These findings highlight the importance of PRC1 subcomplexes in silencing lineage-specific genes and ensuring robust maintenance of ESC identity.
Article
Immunology
Yin Xia, Linlin Zhou, Hung-Chih Yang, Chen-Wei Yu
Summary: This study aimed to analyze the immune characteristics of liver cancer and its association with patient characteristics and clinical outcomes. The results showed that high expression of myeloid-derived suppressor cells (MDSCs) is linked to a decrease in effector T cells in liver tumor progression. The CCL5-high subtype was associated with improved overall survival and disease-free survival.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Min-chun Jiang, Huan-yu Ding, Yu-hong Huang, Chak Kwong Cheng, Chi Wai Lau, Yin Xia, Xiao-qiang Yao, Li Wang, Yu Huang
Summary: Atherosclerotic diseases are a major cause of adult mortality and strain healthcare systems worldwide. A study found that the drug thioridazine can inhibit YAP activity and alleviate endothelial inflammation and atherosclerosis. Thioridazine was shown to have anti-inflammatory effects mediated by inhibiting YAP and regulating RhoA. Furthermore, thioridazine reduced atherosclerosis in two mouse models. This research suggests the potential of repurposing thioridazine for treating atherosclerotic diseases.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Immunology
Enyi Zhu, Yang Liu, Ming Zhong, Yu Liu, Xi Jiang, Xiaorong Shu, Na Li, Hui Guan, Yin Xia, Jinhong Li, Hui-yao Lan, Zhihua Zheng
Summary: The study reveals that neurokinin-1 receptor (NK-1R) promotes renal inflammation and fibrosis in chronic kidney disease (CKD), suggesting that NK-1R could be a potential therapeutic target for CKD patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Lixia Dong, Huaqi Liao, Linchun Zhao, Jingnan Wang, Congcong Wang, Bowen Wang, Yanqi Sun, Lijun Xu, Yin Xia, Shizhang Ling, Xin Lou, Jinzhong Qin
Summary: The interaction between H3K9 methylation writers and readers is crucial for maintaining the identity of embryonic stem cells.
Article
Biochemistry & Molecular Biology
Lijing Kang, Juanjuan Yi, Chi-Wai Lau, Lei He, Qinghua Chen, Suowen Xu, Jun Li, Yin Xia, Yuanting Zhang, Yu Huang, Li Wang
Summary: Hyperglycemia activates Yes-associated protein 1 (YAP) by suppressing AMPK activity, leading to obesity-associated endothelial dysfunction and inflammation. Metformin improves vascular dysfunction by activating AMPK and promoting YAP phosphorylation.
Article
Physiology
Yang Liu, Chunhua Xu, Jinhong Li, Yu Zhang, Xiaohua Wang, Yang Wang, Jinzhong Qin, Zhihua Zheng, Yin Xia
Summary: Chronic kidney disease (CKD) is a major health problem characterized by kidney fibrosis. In this study, the researchers investigated the role of the Hippo/yes-associated protein (YAP) pathway in CKD and found that YAP regulates activator protein-1 (AP-1) expression, with Fosl1 being the primary target in renal tubular cells. These findings provide new insights into the underlying mechanisms of CKD and may have implications for potential therapeutic targets.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Urology & Nephrology
Yu Zhang, Huihui Huang, Yonglun Kong, Chunhua Xu, Liujiang Dai, Xiaoqiang Geng, Yujie Deng, Yang Wang, Yang Liu, Chenling Meng, Xiaoyi Zhang, Jinhong Li, Jinzhong Qin, Bo Feng, Kingston Kinglun Mak, Li Wang, Yu Huang, Weidong Wang, Hui-Yao Lan, Baoxue Yang, Hua A. Jenny Lu, Yin Xia
Summary: Final urine volume and concentration are determined by the regulation of water channels aquaporin (AQP)-2, -3, and -4 in the collecting duct. The Hippo/Yes-associated protein 1 (YAP) pathway and its interaction with various transcription factors play a crucial role in the transcriptional regulation of these AQPs. YAP promotes the transcription of Aqp2 and Aqp4, interacts with GATA2, GATA3, and NFATc1 to control Aqp2 expression, and exploits overlapping mechanisms with Aqp-2, -3, and -4 for their baseline regulation.
KIDNEY INTERNATIONAL
(2023)