Article
Chemistry, Medicinal
Juliana P. Vago, Natalia Valdrighi, Esmeralda N. Blaney-Davidson, Daniel L. A. H. Hornikx, Margot Neefjes, Maria E. Barba-Sarasua, Nathalie G. M. Thielen, Martijn H. J. van den Bosch, Peter M. van der Kraan, Marije I. Koenders, Flavio A. Amaral, Fons A. J. van de Loo
Summary: This study investigated the anti-inflammatory effects of Gas6, a TAM receptor ligand, in synovial fibroblasts from osteoarthritis (OA) patients. Gas6 was found to reduce the levels of inflammatory markers, and its effects depended on the activation of the Axl receptor and the induction of SOCS1/3.
Article
Rheumatology
M. Bellan, M. Quaglia, A. Nerviani, D. Mauro, M. Lewis, F. Goegan, A. Gibbin, S. Pagani, L. Salmi, L. Molinari, L. M. Castello, G. C. Avanzi, V Cantaluppi, M. Pirisi, P. P. Sainaghi, C. Pitzalis
Summary: The study found that plasma concentrations of Gas6, sAxl, and sMer are associated with the severity of lupus nephritis in patients with systemic lupus erythematosus. These biomarkers are directly correlated with creatinine and daily proteinuria, and inversely related to creatinine clearance. Additionally, the level of proteinuria is positively correlated with the plasma concentrations of Gas6, sAxl, and sMer.
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Agata Poswiata, Kamila Kozik, Marta Miaczynska, Daria Zdzalik-Bielecka
Summary: This study reveals the coupling between AXL endocytic trafficking and AKT signaling upon GAS6 stimulation, and provides a rationale for pharmacological inhibition of AXL in antiviral therapy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Manuela Rizzi, Stelvio Tonello, Davide D'Onghia, Pier Paolo Sainaghi
Summary: Gas6 is a widely expressed protein involved in various biological processes. It serves as the main ligand for TAMs, and its activation plays a crucial role in modulating inflammatory responses and fibrotic evolution. This review focuses on Gas6/TAM axis activation in SARS-CoV-2 infection and highlights the potential therapeutic benefits of targeting Axl, a receptor member of TAMs, in COVID-19 management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hyuncheol Jung, Se Young Lee, Seongjoon Lim, Hyeong Ryeol Choi, Yeseong Choi, Minjin Kim, Segi Kim, Yujean Lee, Kyung Ho Han, Won-Suk Chung, Chan Hyuk Kim
Summary: In this study, an engineered protein was developed to induce the engulfment of amyloid-beta (Aβ), leading to improved behavior in Alzheimer's disease mouse models. This protein showed better outcomes compared to conventional antibody therapy, without causing increased inflammation or vascular pathology.
Article
Multidisciplinary Sciences
Daria Zdzalik-Bielecka, Agata Poswiata, Kamila Kozik, Kamil Jastrzebski, Kay Oliver Schink, Marta Brewinska-Olchowik, Katarzyna Piwocka, Harald Stenmark, Marta Miaczynska
Summary: The study identified an interactome of AXL and its associations with proteins regulating actin dynamics. GAS6-mediated AXL activation triggered actin remodeling and macropinocytosis, promoting the survival of cancer cells under glutamine-deprived conditions. AXL activation by GAS6 drove invasion of cancer cells through actin-driven cytoskeletal rearrangements.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Microbiology
Daria Apostolo, Luciana L. Ferreira, Alice Di Tizio, Barbara Ruaro, Filippo Patrucco, Mattia Bellan
Summary: The tyrosine kinase receptors of the TAM family and their ligand Gas6 play a crucial role in innate immunity and inflammatory response. The Gas6/TAM system is involved in the recognition of apoptotic debris by immune cells, which has been exploited by viruses like COVID-19 for cell entry and infection. Understanding the mechanisms underlying COVID-related fibrosis, particularly in the lungs, is still limited, and this review aims to integrate the current knowledge of the Gas6/TAM axis with the pathophysiological mechanisms of COVID-19, focusing on the development of a fibrotic phenotype.
Article
Biochemistry & Molecular Biology
Francesco Gavelli, Luca Molinari, Marco Baldrighi, Livia Salmi, Filippo Mearelli, Nicola Fiotti, Filippo Patrucco, Chiara Airoldi, Mattia Bellan, Pier Paolo Sainaghi, Salvatore Di Somma, Enrico Lupia, Efrem Colonetti, Maria Lorenza Muiesan, Gianni Biolo, Gian Carlo Avanzi, Luigi Mario Castello
Summary: This study found that measuring the concentration of sMer and Gas6 at the emergency department did not predict mortality, but these biomarkers were associated with acute kidney injury, thrombocytopenia, deranged prothrombin time-international normalized ratio, and sepsis-induced coagulopathy, suggesting a role in predicting sepsis-related organ damage.
Article
Gastroenterology & Hepatology
Oltin-Tiberiu Pop, Anne Geng, Emilio Flint, Arjuna Singanayagam, Caner Ercan, Lucia Possamai, Vishal C. Patel, Patrizia Kuenzler, Marie -Anne Meier, Savas Soysal, Petr Hruz, Otto Kollmar, Kate C. Tatham, Josie K. Ward, Beat Muellhaupt, Achim Weber, Julia Wendon, Jan Hendrik Niess, Markus Heim, David Semela, Christopher Weston, Charalambos G. Antoniades, Luigi Maria Terracciano, Evangelos Triantafyllou, Robert G. Brenig, Christine Bernsmeier
Summary: This study found that AXL is expressed on tissue macrophages in patients with cirrhosis, but not on tissue-infiltrating liver macrophages, hepatocytes, and sinusoidal endothelial cells. The expression of AXL decreases significantly with cirrhosis progression and is negatively correlated with liver function and C-reactive protein. AXL-expressing liver macrophages show high expression of CD68, HLA-DR, CD16, and CD206. Additionally, AXL expression decreases on gut and peritoneal macrophages in cirrhotic patients but increases in regional lymph nodes. These findings suggest an important role for AXL in the regulation of hepatic immune homeostasis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Cell Biology
Yunxiang Zhou, Yali Wang, Hailong Chen, Yanyan Xu, Yi Luo, Yongchuan Deng, Jianmin Zhang, Anwen Shao
Summary: TAM receptors play a critical role in tumor development, but inhibiting TAM signaling may not always be beneficial in the tumor immune microenvironment and could impact anti-tumor immunity. In glioblastoma, TAM receptors may have potential anti-tumor effects, suggesting a dual role in cancer progression.
CELL COMMUNICATION AND SIGNALING
(2021)
Review
Oncology
Kaichi Kaneko, Hao Chen, Matthew Kaufman, Isaak Sverdlov, Emily M. Stein, Kyung-Hyun Park-Min
Summary: Osteonecrosis is a complex and devastating complication of systemic lupus erythematosus, with variable prevalence in SLE patients. The use of high-dose glucocorticoid therapy is strongly associated with the development of osteonecrosis in SLE patients, although the exact pathophysiology and risk factors for osteonecrosis in this population are not fully understood.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Valeria Rella, Cinzia Rotondo, Alberto Altomare, Francesco Paolo Cantatore, Addolorata Corrado
Summary: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations. Dysregulation of the immune system due to genetic, hormonal, and environmental factors can lead to various complications, including bone involvement such as osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Paul Curtiss, Amanda M. Walker, Benjamin F. Chong
Summary: This study reviewed patient cohorts and populations to investigate the progression of cutaneous lupus to systemic lupus. The study found variations in the progression rates between adult and pediatric groups, which were attributed to differences in patient populations, study design, diagnostic criteria, and follow-up time. Risk factors associated with the development of systemic lupus included positive anti-nuclear antibodies, hematologic abnormalities, and a higher number of lupus classification criteria at baseline.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wook-Young Baek, Yang-Seon Choi, Sang-Won Lee, In-Ok Son, Ki-Woong Jeon, Sang-Dun Choi, Chang-Hee Suh
Summary: Toll-like receptors (TLRs) play a crucial role in the innate immune system, with studies showing their regulatory effects on immune and inflammatory diseases. A TLR inhibitor peptide (TIP1) was found to suppress downstream signaling mediated by TIR domain-containing adapters, suggesting its potential as a candidate for treating systemic lupus erythematosus (SLE).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Shunxiang Li, Huihua Ding, Ziheng Qi, Jing Yang, Jingyi Huang, Lin Huang, Mengji Zhang, Yuanjia Tang, Nan Shen, Kun Qian, Qiang Guo, Jingjing Wan
Summary: Serum metabolic fingerprints can be used for disease diagnosis and biomarker discovery. By analyzing the serum metabolic fingerprints of systemic lupus erythematosus (SLE) patients and healthy controls, early diagnosis and precision medicine for SLE can be achieved. This study identified the unique metabolic pattern of SLE patients and screened out a panel of metabolic biomarkers.
Article
Immunology
Yuxuan Zhen, Stephen O. Priest, Wen-Hai Shao
JOURNAL OF IMMUNOLOGY
(2016)
Article
Immunology
Yuxuan Zhen, Iris J. Lee, Fred D. Finkelman, Wen-Hai Shao
JOURNAL OF AUTOIMMUNITY
(2018)
Article
Immunology
Wen-Hai Shao, Yuxuan Zhen, Fred D. Finkelman, Philip L. Cohen
JOURNAL OF AUTOIMMUNITY
(2014)
Article
Cell Biology
David E. Adams, Wen-Hai Shao
Summary: This article discusses the epigenetic alterations associated with systemic lupus erythematosus (SLE) and their role in the pathophysiology of the disease. It also summarizes the therapeutic potential of the new findings.
Article
Cell Biology
David E. Adams, Yuxuan Zhen, Xiaoyang Qi, Wen-Hai Shao
Summary: Axl receptor tyrosine kinase plays a role in inflammatory renal diseases by promoting glomerular proliferation. The expression of Axl in the kidney is regulated by transcription factors and secondary structures. MiRNA-34a negatively regulates Axl expression.
Article
Rheumatology
Yuxuan Zhen, Roger D. Smith, Fred D. Finkelman, Wen-Hai Shao
ARTHRITIS RESEARCH & THERAPY
(2020)
