Article
Biochemistry & Molecular Biology
Asfia Soomro, Jackie Trink, Kian O'Neil, Renzhong Li, Safaa Naiel, Bo Gao, Kjetil Ask, Joan C. Krepinsky
Summary: This study identifies two novel activators of RhoA/ROCK signaling in diabetic kidneys, activins and cell-surface GRP78, which promote fibrosis and disease progression. Inhibiting these factors may offer a potential strategy for attenuating DKD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Behavioral Sciences
RuoLan Cai, YangYang Wang, ZhenTing Huang, Qian Zou, YinShuang Pu, Changyin Yu, Zhiyou Cai
Summary: ROCK activation can promote the occurrence of Alzheimer's disease and may involve a positive feedback loop between Aβ and ROCK. Additionally, ROCK can also promote the formation of neurofibrillary tangles and exacerbate neuroinflammatory responses.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Cell Biology
Zeina Harhous, Wissam H. Faour, Nabil El Zein
Summary: The study revealed that VIP induced activation of phospho-AKT and phospho-ERK1/2 levels in macrophages in a GTP-RhoA-GTPase-dependent manner. VIP also increased intracellular release of H2O2 and calcium through PLC and GTP-RhoA-GTPase, and induced the expression of CD11b, CD35, CD66, and MMP9. Furthermore, VIP activated P38 MAPK through the cAMP/PKA pathway but independently of PLC and RhoA signaling, with these effects mediated via the FPRL1 receptor.
INFLAMMATION RESEARCH
(2021)
Article
Cell Biology
Xiaoqi Han, Siyuan Jiang, Yinmin Gu, Lihua Ding, Enhao Zhao, Dongxing Cao, Xiaodong Wang, Ya Wen, Yongbo Pan, Xin Yan, Liqiang Duan, Minxuan Sun, Tao Zhou, Yajuan Liu, Hongbo Hu, Qinong Ye, Shan Gao
Summary: In this study, it was found that HUNK inhibits EMT and metastasis of CRC cells through its kinase-dependent interaction with GEF-H1. HUNK directly phosphorylates GEF-H1 at serine 645, leading to activation of RhoA and subsequent phosphorylation of LIMK-1/CFL-1, resulting in stabilization of F-actin and inhibition of EMT. Clinically, decreased levels of HUNK expression and phosphorylation of GEF-H1 at serine 645 were observed in CRC tissues with metastasis, indicating their potential as biomarkers for metastasis.
CELL DEATH & DISEASE
(2023)
Article
Chemistry, Medicinal
Olmo Martin-Camara, Angel Cores, Pilar Lopez-Alvarado, J. Carlos Menendez
Summary: The morphology of synaptic spines is controlled by Rac1, Cdc42, and RhoA, with RhoA/ROCK playing a crucial role in stabilizing actin formation and preventing the generation of new protrusions. The RhoA/ROCK pathway influences plasticity processes and is implicated in various brain-related pathologies, highlighting its importance in drug discovery for neurodegenerative diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cardiac & Cardiovascular Systems
Michael Hauke, Robert Eckenstaler, Anne Ripperger, Anna Ender, Heike Braun, Ralf A. Benndorf
Summary: This study demonstrates that increased RhoA activity has the potential to trigger endothelial dysfunction and anti-angiogenic effects independently of its well-known downstream effectors ROCK and LIMK.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Biochemistry & Molecular Biology
Hiroshi Senoo, Daisuke Murata, May Wai, Kenta Arai, Wakiko Iwata, Hiromi Sesaki, Miho Iijima
Summary: AKT, a serine/threonine kinase, plays a crucial role in metabolism, cell growth, and cytoskeletal dynamics, and is activated by PDK1 and mTORC2. Research has uncovered that insulin activates mTORC2 towards AKT by forming a supercomplex KARATE with KRAS4B and RHOA GTPases, revealing a fundamental mechanism in insulin-regulated glucose homeostasis.
Review
Cardiac & Cardiovascular Systems
Steven Marston, Jose Renato Pinto
Summary: In cardiac muscle, the action of adrenaline on beta 1 receptors is essential for enhancing contractility, heart rate, and relaxation through PKA activation. Lusitropy plays a crucial role in shortening the heartbeat during increased heart rate. PKA phosphorylates TnI and PLB, leading to faster relaxation and Ca2+ removal. This review examines the relationship between decreased lusitropy and cardiac dysfunction, discusses the impact of mutations in PLB and thin filament proteins, and evaluates the therapeutic potential of restoring suppressed lusitropy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Oncology
Yongtao Yang, Lianyong Li, Huan He, Mengyang Shi, Lanying He, Shuwen Liang, Jun Qi, Weiqing Chen
Summary: Numb regulates cell proliferation, differentiation, migration, and apoptosis through the RhoA/ROCK signaling pathway in colorectal cancer. Its expression is correlated with prognosis and provides a new theoretical molecular basis for understanding the pathogenesis of colorectal cancer.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Environmental Sciences
Lianxin Li, Jinge Xin, Hesong Wang, Yadong Wang, Weiqi Peng, Ning Sun, Haonan Huang, Yanxi Zhou, Xingmei Liu, Yu Lin, Jing Fang, Bo Jing, Kangcheng Pan, Yan Zeng, Dong Zeng, Xiang Qin, Yang Bai, Xueqin Ni
Summary: Fluoride is a common contaminant that poses challenges to animal and human health. This study investigates the role of the cytoskeleton in fluoride-induced barrier dysfunction and provides potential therapeutic targets for fluoride-induced intestinal injury.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Review
Cell Biology
Sissel Ida Schmidt, Morten Blaabjerg, Kristine Freude, Morten Meyer
Summary: RhoA, a small GTPase involved in multiple signal transduction pathways, plays a crucial role in neurodegenerative diseases. Understanding the regulation of RhoA and its downstream cellular functions is important for elucidating the mechanisms of neurodegenerative diseases and exploring potential therapeutic interventions.
Article
Ophthalmology
Tomokazu Fujimoto, Saori Sato-Ohira, Hidenobu Tanihara, Toshihiro Inoue
Summary: This study investigated the effects of RhoA signaling on the phagocytosis of trabecular meshwork (TM) cells, revealing that RhoA signal pathway plays a critical role in regulating the phagocytic activity of TM cells.
CURRENT EYE RESEARCH
(2021)
Article
Behavioral Sciences
Yingchun Xiang, Yumiao Niu, Yacong Xie, Shishuo Chen, Feng Zhu, Weida Shen, Ling-Hui Zeng
Summary: The study investigated the phosphorylation levels of the RhoA/Rho kinase pathway in response to KA treatment, and found that KA induces activation of the pathway leading to inhibition of neurite outgrowth. Pretreatment with fasudil reversed this effect, suggesting that inhibiting the RhoA/Rho kinase pathway may be a potential treatment for seizure-induced neurite injury.
BRAIN AND BEHAVIOR
(2021)
Review
Pharmacology & Pharmacy
Robert Eckenstaler, Michael Hauke, Ralf A. Benndorf
Summary: RhoA, RhoB, and RhoC are key regulators of signal transduction in cell biology and have significant roles in tumor biology and vascular biology, regulating various cellular processes and disease pathogenesis.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Peng-cheng Tu, Ya-lan Pan, Zhong-qing Liang, Guang-lu Yang, Cheng-jie Wu, Liang Zeng, Li-ning Wang, Jie Sun, Meng-min Liu, Yong-feng Yuan, Yang Guo, Yong Ma
Summary: Macrophages play a crucial role in inflammatory diseases, and mechanical load can influence their function and enhance inflammatory responses. This study found that mechanical stretch can regulate macrophage polarization and enhance inflammation in vitro.
BIOMED RESEARCH INTERNATIONAL
(2022)
Article
Hematology
Man K. S. Lee, Michael J. Kraakman, Dragana Dragoljevic, Nordin M. J. Hanssen, Michelle C. Flynn, Annas Al-Sharea, Gopalkrishna Sreejit, Camilla Bertuzzo-Veiga, Olivia D. Cooney, Fatima Baig, Elizabeth Morriss, Mark E. Cooper, Emma C. Josefsson, Benjamin T. Kile, Prabhakara R. Nagareddy, Andrew J. Murphy
Summary: Reducing platelet numbers through targeting the antiapoptotic protein Bcl-x(L) can effectively decrease atherosclerosis and reduce cardiovascular disease risk in diabetes, as demonstrated in genetic and pharmacological approaches in this study.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jillian Johnson, Robert M. Jaggers, Sreejit Gopalkrishna, Albert Dahdah, Andrew J. Murphy, Nordin M. J. Hanssen, Prabhakara R. Nagareddy
Summary: Neutrophil behavior and function are altered by hyperglycemia associated with diabetes, leading to increased production of ROS and inflammation, which in turn increases the risk of cardiovascular diseases. The focus of treatment is shifting towards mitigating glucotoxicity and targeting cellular dysfunction downstream of hyperglycemia.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Review
Cardiac & Cardiovascular Systems
Sreejit Gopalkrishna, Jillian Johnson, Robert M. Jaggers, Albert Dahdah, Andrew J. Murphy, Nordin M. J. Hanssen, Prabhakara R. Nagareddy
Summary: Neutrophils play a dual role in inflammation and wound healing, causing tissue damage while also facilitating healing. Recent studies have revealed their transcriptional activity and ability to influence other cells through cargo release. They have emerged as important regulators in cardiovascular diseases and could be potential targets for therapeutic strategies.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Gopalkrishna Sreejit, Sunil K. Nooti, Robert M. Jaggers, Baskaran Athmanathan, Ki Ho Park, Annas Al-Sharea, Jillian Johnson, Albert Dahdah, Man K. S. Lee, Jianjie Ma, Andrew J. Murphy, Prabhakara R. Nagareddy
Summary: Acute myocardial infarction leads to the accumulation of neutrophils in the bone marrow, where they release IL-1 beta and promote granulopoiesis through specific signaling pathways. Pharmacological and genetic strategies can inhibit this process and improve cardiac function.
Letter
Cardiac & Cardiovascular Systems
Prabhakara R. Nagareddy, Gopalkrishna Sreejit
Letter
Cardiac & Cardiovascular Systems
Prabhakara R. Nagareddy, Gopalkrishna Sreejit
Review
Cell Biology
Albert Dahdah, Jillian Johnson, Sreejit Gopalkrishna, Robert M. M. Jaggers, Darren Webb, Andrew J. J. Murphy, Nordin M. J. Hanssen, Beatriz Y. Y. Hanaoka, Prabhakara R. R. Nagareddy
Summary: The body's inflammatory response requires immune cells to migrate to the site of inflammation, and this process is facilitated by the vasculature. Neutrophils are important leukocytes involved in this response. This review focuses on the mechanisms of leukocyte migration, particularly neutrophil migration, in conditions such as diabetes and cardiovascular disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Farshad Babaeijandaghi, Ryan Cheng, Nasim Kajabadi, Hesham Soliman, Chih-Kai Chang, Josh Smandych, Lin Wei Tung, Reece Long, Amirhossein Ghassemi, Fabio M. Rossi
Summary: This study identified three populations of skeletal muscle-resident myelomonocytic cells, including macrophages positive for LYVE1 and TIM4, macrophages negative for TIM4, and dendritic cells positive for CD11C and MHCII. Lineage-tracing experiments showed that TIM4(-) macrophages were replenished from the blood, while TIM4(+) macrophages had local self-renewal capacity. The study revealed the unique function of self-renewing resident macrophages in clearing apoptotic cells after extensive acute injury, as well as their role in protecting muscle against injury in a mouse model of muscular dystrophy.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Farshad Babaeijandaghi, Adrianna Paiero, Reece Long, Lin Wei Tung, Shannon Percival Smith, Ryan Cheng, Joshua Smandych, Nasim Kajabadi, Chih-Kai Chang, Amirhossein Ghassemi, William D. M. Kennedy, Hesham Soliman, Peter W. Schutz, Fabio M. Rossi
Summary: In this study, it is found that natural killer (NK) cells are the main source of IFN gamma in regenerating muscle. The production of IFN gamma is also limited to a small population of T cells. However, NK cells do not play a major role in muscle regeneration. The absence of IFN gamma per se has no effect on muscle regeneration, but its role is partially unmasked when TNF alpha is also neutralized.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Albert Dahdah, Robert M. Jaggers, Gopalkrishna Sreejit, Jillian Johnson, Babunageswararao Kanuri, Andrew J. Murphy, Prabhakara R. Nagareddy
Summary: Smoking is one of the leading preventable causes of death worldwide, and it has negative effects on major organs and the immune system. Although electronic cigarettes reduce the negative effects of burning tobacco, the delivery of nicotine still has adverse health effects. Understanding the pathological mechanisms of smoking is important for preventing cardiovascular and immune diseases.
Article
Cell Biology
Elena Groppa, Paolo Martini, Nima Derakhshan, Marine Theret, Morten Ritso, Lin Wei Tung, Yu Xin Wang, Hesham Soliman, Mark Stephen Hamer, Laura Stankiewicz, Christine Eisner, Le Neve Erwan, Chihkai Chang, Lin Yi, Jack H. Yuan, Sunny Kong, Curtis Weng, Josephine Adams, Lucas Chang, Anne Peng, Helen M. Blau, Chiara Romualdi, Fabio M. V. Rossi
Summary: Efficient regeneration requires coordination between multiple cell types. This study analyzes the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells to understand the intercellular networks involved in regeneration. The findings identify VEGFA-driven endothelial engagement as a key differentiating feature in successful and failed regeneration models. Additionally, the study reveals that multiple cell types simultaneously produce most secreted signals, including VEGFA. Deleting VEGFA from stromal and myogenic progenitors shows that spatial compartmentalization of signaling plays a crucial role in intercellular communication networks.
Meeting Abstract
Cardiac & Cardiovascular Systems
Gopalkrishna Sreejit, Sunil Nooti, Robert Jaggers, Jillian Johnson, Jianjie Ma, Andrew Murphy, Prabhakara R. Nagareddy
CIRCULATION RESEARCH
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Albert Dahdah, Ki H. Park, Gopalkrishna Sreejit, Robert Jaggers, Jillian Johnson, Prabhakara R. Nagareddy
CIRCULATION RESEARCH
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Naresh Kumar, Matthew J. Pestrak, Qian Wu, Sheri Dellos-Nolan, Rajnikant Shukla, Cortney F. Mitchem, Lianbo Yu, William Lafuse, Prabhakara R. Nagareddy, Latha P. Ganesan, Daniel Wozniak, Murugesan V. Rajaram
CIRCULATION RESEARCH
(2022)
Meeting Abstract
Endocrinology & Metabolism
L. Bernier, J. Hefendehl, W. Scott, L. Tung, H. Soliman, L. Dissing-Olesen, J. Hofmann, F. Rossi, M. Underhill, B. MacVicar
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)