Article
Cell Biology
Ololade Ogunsina, Richa Banerjee, Luz A. A. Knauer, Ying Yang
Summary: The study found that FOXO1 inhibits the formation of lymphatic valves, making it a potential target for treating congenital lymphedema. The use of the FOXO1 inhibitor AS1842856 in both in vitro and in vivo models resulted in a significant increase in the expression levels of valve-forming genes and activation of beta-catenin, promoting lymphatic valve formation. These findings suggest that pharmacological inhibition of FOXO1 could be an effective strategy for resolving valve defects in congenital lymphedema.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Li Zhong, Qing Liu, Qiaofeng Liu, Shikai Zhang, Yongbing Cao, Dehua Yang, Ming-Wei Wang
Summary: The research revealed that W2476 promotes the competitive binding of FOXO1 with the ChoRE-binding protein/Mlx complexes, hindering the acetylation process of the TXNIP promoter, and ultimately reducing TXNIP transcription.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Review
Physiology
Fumiko Itoh, Tetsuro Watabe
Summary: Transforming growth factor (TGF)-beta and its family members play a crucial role in the development and maintenance of the lymphatic vascular system, which is involved in various physiological and pathological processes such as immune cell trafficking and tumor metastasis.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jan Kazenwadel, Parvathy Venugopal, Anna Oszmiana, John Toubia, Luis Arriola-Martinez, Virginia Panara, Sandra G. Piltz, Chris Brown, Wanshu Ma, Andreas W. Schreiber, Katarzyna Koltowska, Samir Taoudi, Paul Q. Thomas, Hamish S. Scott, Natasha L. Harvey
Summary: In this study, a novel enhancer element responsible for regulating Prox1 expression in lymphatic endothelial cells was identified. Genome editing of this enhancer resulted in perinatal death and profound lymphatic vascular defects in mutant mice. The mutant mice also exhibited altered gene expression profiles and acquired the ability to generate hematopoietic cells. These findings demonstrate the importance of this enhancer in controlling lymphatic endothelial cell identity and reveal the previously unknown hemogenic capacity of the lymphatic endothelium.
Article
Medicine, Research & Experimental
Joshua P. Scallan, Luz A. Knauer, Huayan Hou, Jorge A. Castorena-Gonzalez, Michael J. Davis, Ying Yang
Summary: Research identified Foxo1 as a key transcription factor repressing lymphatic valve formation, deletion of which promoted valve formation. Rescue experiments and quantitative analysis confirmed that deletion of Foxo1 completely restored lymphatic valve number and function. These findings establish Foxo1 as a new clinical target for treating patients with congenital lymphedema.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Yaping Meng, Tong Lv, Junfeng Zhang, Weimin Shen, Lifang Li, Yaqi Li, Xin Liu, Xing Lei, Xuguang Lin, Hanfang Xu, Anming Meng, Shunji Jia
Summary: This study reveals the involvement of the Efnb2-Ephb4-Rasa1 regulated Erk signaling axis in lymphatic valve development. The inhibition of Erk signaling during valve cell specification and the opposite roles of Erk signaling in lymphatic vessel development and lymphatic valve formation are demonstrated. The findings provide insights into the molecular mechanism of lymphatic valve formation and have implications for the treatment of lymphatic disorders.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Tomoyuki Tanaka, Akira Takahashi, Yutaka Kobayashi, Masanori Saito, Sun Xiaolong, Chen Jingquan, Yoshiaki Ito, Tsuyoshi Kato, Hiroki Ochi, Shingo Sato, Toshitaka Yoshii, Atsushi Okawa, Peter Carlsson, Hiroyuki Inose
Summary: This study uncovers the crucial role of FOXF2 in the differentiation of stem cells into bone-producing cells, providing insight into the pathogenesis of bone-related diseases such as osteoporosis and non-healing fractures.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ana Luisa De Sousa-Coelho, Mar Gacias, Brian T. O'Neill, Joana Relat, Wolfgang Link, Diego Haro, Pedro F. Marrero
Summary: The study found that FOXO1 is a protein that interacts with PPARa and can inhibit its activity on the FGF21 gene promoter, thereby regulating FGF21 expression. This suggests that FOXO1 is an important factor in the regulation of FGF21.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Environmental Sciences
Mingsi Deng, Jia Luo, Heng Cao, Yong Li, Liangjian Chen, Gengyan Liu
Summary: This study aimed to explore the biological function of METTL14 in osteoclast formation and its related mechanisms. It found that METTL14 inhibits osteoclastogenesis and bone resorption through enhancing GPX4 stability via an m6A-HuR dependent mechanism. Targeting METTL14 might be a novel promising treatment strategy for osteoporosis.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Biology
Juil Kim, Yuseok Moon
Summary: Kim and Moon discovered that the transcription factor PRDM1 is upregulated in colorectal cancer (CRC) cells in response to ribosomal dysfunction, leading to chemoresistance through the IGF signaling pathway. They also found that PRDM1 promotes cancer cell stemness and survival, providing insights into environmental stress-mediated signaling in CRC.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Simon Stritt, Katarzyna Koltowska, Taija Makinen
Summary: The lymphatic vasculature is not only a drainage system, but also directly involved in regulating immunity and organ growth, with important roles in development mechanisms and functional characteristics. Understanding the mechanisms that maintain lymphatic vessel integrity in adult tissues and control vessel repair and regeneration is crucial for comprehending disease-related vascular changes.
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Natalie R. Harris, Natalie R. Nielsen, John B. Pawlak, Amir Aghajanian, Krsna Rangarajan, D. Stephen Serafin, Gregory Farber, Danielle M. Dy, Nathan P. Nelson-Maney, Wenjing Xu, Disha Ratra, Sophia H. Hurr, Li Qian, Joshua P. Scallan, Kathleen M. Caron
Summary: This study reveals the essential role of VE-cadherin in the development and maintenance of cardiac lymphatics and its impact on lymphangiogenic signaling pathways. Surprisingly, despite the regression of cardiac lymphatics, Cdh5(flox/flox);Prox1CreER(T2) mice exhibited preserved cardiac function at baseline and after myocardial infarction compared with control mice. Mechanistically, loss of VE-cadherin leads to aberrant cellular internalization of VEGFR3, impairing downstream processes such as cellular proliferation.
CIRCULATION RESEARCH
(2022)
Article
Cell Biology
Pan Cai, Yan Lu, Zhifeng Yin, Xiuhui Wang, Xiaoxiao Zhou, Zhuokai Li
Summary: The study used bioinformatics and an in vitro cellular model to investigate the mechanisms underlying the beneficial effects of baicalein (BN) against glucocorticoid-induced osteoporosis. Analysis revealed BN-targeted genes enriched in KEGG pathways, with common pathways related to osteoporosis. Baicalein was found to suppress osteoporosis through an AKT/FOXO1 signaling pathway, partially reversing glucocorticoid-induced osteoporosis in MC3T3-E1 cells.
Article
Biochemical Research Methods
Samantha Kraus, Esak Lee
Summary: This study developed a human lymphatic vessel chip to investigate the effects of acute and chronic inflammation on primary lymphatic valve function. The results showed that acute inflammation impeded lymphatic drainage, while chronic inflammation increased lymphatic permeability. This study reveals distinct mechanisms of primary lymphatic valve dysfunction in acute and chronic inflammation.
Article
Developmental Biology
Nanbing Li-Villarreal, Rebecca Lee Yean Wong, Monica D. Garcia, Ryan S. Udan, Ross A. Poche, Tara L. Rasmussen, Alexander M. Rhyner, Joshua D. Wythe, Mary E. Dickinson
Summary: This study reveals a novel role for FOXO1 as a key transcriptional repressor regulating both pre-flow arterial specification and subsequent vessel remodeling within the murine YS.
Article
Cell Biology
Satoshi Shibata, Tsubasa Kawanai, Takayuki Hara, Asuka Yamamoto, Taro Chaya, Yasunori Tokuhara, Chinami Tsuji, Manabu Sakai, Taro Tachibana, Shinobu Inagaki
JOURNAL OF CELL SCIENCE
(2016)