Article
Cell Biology
Yu Zhang, Moises Hernandez, Jonathan Gower, Nolan Winicki, Xena Morataya, Sebastian Alvarez, Jason X-J Yuan, John Shyy, Patricia A. Thistlethwaite
Summary: This study found that the NOTCH3 pathway plays a crucial role in controlling vascular smooth muscle cell proliferation and differentiation in the pulmonary arterial tree. In pulmonary arterial hypertension (PAH) patients, JAGGED-1 is overexpressed in small pulmonary artery smooth muscle cells and selectively activates NOTCH3 signaling, leading to increased cellular proliferation. On the other hand, DELTA-LIKE 4 inhibits NOTCH3 signaling and retards smooth muscle cell proliferation. A new monoclonal antibody was developed to block JAGGED-1-induced cleavage of NOTCH3 and successfully reversed pulmonary hypertension in animal models without toxic side effects. Targeting JAGGED-1 activation of NOTCH3 may be an effective and safe strategy for treating PAH.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jian Wang, Xin Yan, Wei Feng, Qingting Wang, Wenhua Shi, Limin Chai, Qianqian Zhang, Yuqian Chen, Jin Liu, Zhan Qu, Xinming Xie, Manxiang Li
Summary: S1P promotes PASMC proliferation by activating the S1PR2/STAT3/miR-135b/beta-transduction repeat-containing protein/YAP/Notch3 pathway.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Integrative & Complementary Medicine
Yongli Tan, Yemu Zhu
Summary: This study investigates the role and mechanism of Notch3 in a hypoxia-induced model of pulmonary hypertension. The results show that Notch3 overexpression can reduce angiogenesis and proliferation in pulmonary artery endothelial cells, and improve hypoxia-induced pulmonary artery hypertension.
ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Laura Vera, Paula Garcia-Olloqui, Eva Petri, Ana Cristina Vinado, Pablo S. Valera, Zurine Blasco-Iturri, Isabel A. Calvo, Itziar Cenzano, Clemens Ruppert, Javier J. Zulueta, Felipe Prosper, Borja Saez, Ana Pardo-Saganta
Summary: The study highlights the crucial role of Notch3 in lung fibrosis, with Notch3 deficiency offering protection by reducing collagen deposition, decreasing the number of myofibroblasts, and improving lung function. This discovery uncovers a novel mechanism in lung fibrogenesis and suggests a potential new therapeutic approach for targeting pulmonary fibrosis.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Integrative & Complementary Medicine
Li-Le Wang, Xiao-Li Zhu, Shu-Hua Han, Lu Xu
Summary: This study found that hypoxia promotes the transformation of pulmonary artery endothelial cells into mesenchymal cells by activating the NOTCH3 pathway. The involvement of miR-7-5p in this process was also identified. The research provides a model for understanding the pathogenesis of pulmonary diseases.
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2021)
Article
Medicine, Research & Experimental
Xiao-Qiang Li, Yun-Min Zheng, Jorge Reyes-Garcia, Yong-Xiao Wang
Summary: The study revealed the distinct roles of RyR1 in systemic and pulmonary artery smooth muscle cells, providing clear genetic evidence for their functional importance in muscle contraction and Ca2+ release.
Article
Biochemistry & Molecular Biology
Boyu Chen, Runda Huang, Tianliang Xia, Chunyang Wang, Xiao Xiao, Shunzhen Lu, Xiangfu Chen, Ying Ouyang, Xiaowu Deng, Jingjing Miao, Chong Zhao, Lin Wang
Summary: In this study, the researchers found that IGF2BP3 acts as a key m6A reader in nasopharyngeal carcinoma (NPC) and maintains the stability of NOTCH3 mRNA through an m6A-dependent mechanism, thereby promoting tumor metastasis and enhancing the stemness phenotype. IGF2BP3 is associated with poor prognosis and may serve as a novel prognostic biomarker and therapeutic target in NPC metastasis.
Article
Multidisciplinary Sciences
Shaoyan Gao, Xiaohe Li, Qiuyan Jiang, Qing Liang, Fangxia Zhang, Shuangling Li, Ruiqin Zhang, Jiaoyan Luan, Jingyan Zhu, Xiaoting Gu, Ting Xiao, Hui Huang, Shanshan Chen, Wen Ning, Guang Yang, Cheng Yang, Honggang Zhou
Summary: Our study demonstrates that PKM2 promotes fibrosis progression by interacting with Smad7 and enhancing TGF-beta 1 signaling. Increased expression of PKM2 in the lungs of mice with pulmonary fibrosis contributes to fibrosis development. The PKM2 tetramer enhances TGF-beta 1 signaling by directly binding with Smad7, making it a key factor in fibrosis progression.
Article
Developmental Biology
Sara Bsharat, Emanuela Monni, Tania Singh, Jenny K. Johansson, Kavya Achanta, Ludivine Bertonnier-Brouty, Anja Schmidt-Christensen, Dan Holmberg, Zaal Kokaia, Rashmi B. Prasad, Isabella Artner
Summary: Hormone secretion from pancreatic islets is essential for glucose homeostasis, and loss or dysfunction of islet cells is a hallmark of type 2 diabetes. Maf transcription factors are crucial for establishing and maintaining adult endocrine cell function. Here, we report that MafB deficiency impairs β cell clustering and islet formation, but also coincides with loss of neurotransmitter and axon guidance receptor gene expression.
Article
Multidisciplinary Sciences
Brian Tenner, Jason Z. Zhang, Yonghoon Kwon, Veronica Pessino, Siyu Feng, Bo Huang, Sohum Mehta, Jin Zhang
Summary: FluoSTEPs is a novel class of biosensors that combines self-complementing split green fluorescent protein, CRISPR-mediated knock-in, and fluorescence resonance energy transfer technology to probe compartmentalized signaling dynamics in situ. It can simultaneously highlight endogenous microdomains and report domain-specific, real-time signaling events, including kinase activities, guanosine triphosphatase activation, and second messenger dynamics. FluoSTEPs have been shown to be useful in probing spatiotemporal regulation within endogenous signaling architectures, as demonstrated by a FluoSTEP for 3',5'-cyclic adenosine monophosphate (cAMP) revealing distinct cAMP dynamics within clathrin microdomains in response to stimulation of G protein-coupled receptors.
Article
Chemistry, Multidisciplinary
Bo Li, Krystyna Maruszko, Soo-Kyung Kim, Moon Young Yang, Amy-Doan P. Vo, William A. Goddard
Summary: This study provides a computational analysis of the interactions between GLP-1R-Gs signaling complex and a G protein biased agonist, Exendin P5, and proposes a novel conformation transduction mechanism that enhances Gs protein coupling. The findings offer insights into class B GPCR signaling and can guide the design of more effective therapeutics.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Pathology
Gun-Dong Kim, Hang Pong Ng, E. Ricky Chan, Ganapati H. Mahabeleshwar
Summary: Macrophages play crucial roles in inflammatory vascular diseases, and deficiency of HIF1α may attenuate vascular smooth muscle cells and macrophage abundance, reducing inflammation in stenotic arteries. HIF1α regulates various metabolic and inflammatory signaling pathways in macrophages.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Review
Pathology
Dorothee Schoemaker, Joseph F. Arboleda-Velasquez
Summary: Mutations in the NOTCH3 gene can cause small-vessel disease in humans, including conditions like CADASIL. Different types of NOTCH3 mutations may lead to varying severity of small-vessel disease phenotypes. There is currently a lack of disease-modifying therapies for NOTCH3-associated small-vessel disease, highlighting the need for deeper understanding of underlying molecular mechanisms and defined therapeutic targets.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Oncology
Christen A. Khella, Lucyann Franciosa, Lorna Rodirguez-Rodriguez, Resha Rajkarnikar, Karthikeyan Mythreye, Michael L. Gatza
Summary: In this study, the researchers used a proteogenomic approach to analyze HGSOC tumor samples and identified the upregulation of hematopoietic cell kinase (HCK) expression and signaling in poor prognostic HGSOC patients. Further studies showed that HCK promotes cell proliferation, colony formation, and invasive capacity through CD44 and NOTCH3-dependent signaling. This study suggests that targeting the HCK-CD44-NOTCH3 signaling pathway could be a potential therapeutic opportunity for aggressive and recurrent HGSOC patients.
MOLECULAR CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Asmin Tulpule, Juan Guan, Dana S. Neel, Hannah R. Allegakoen, Yone Phar Lin, David Brown, Yu-Ting Chou, Ann Heslin, Nilanjana Chatterjee, Shriya Perati, Shruti Menon, Tan A. Nguyen, Jayanta Debnath, Alejandro D. Ramirez, Xiaoyu Shi, Bin Yang, Siyu Feng, Suraj Makhija, Bo Huang, Trever G. Bivona
Summary: A membraneless, protein granule-based subcellular structure has been identified to organize RTK/RAS/MAPK signaling in cancer cells, actively signaling within the cytoplasm and activating RAS independently of lipid membranes. The formation of RTK protein granules is critical for oncogenic RAS/MAPK signaling output in these cells. This study reveals a distinct subcellular platform for organizing oncogenic RTK and RAS signaling through higher-order cytoplasmic protein assembly.
Article
Biochemistry & Molecular Biology
Sarah J. Ohle, Asha Anandaiah, Attila J. Fabian, Alan Fine, Darrell N. Kotton
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2012)
Article
Biochemistry & Molecular Biology
Regina Golan-Gerstl, Shulamit B. Wallach-Dayan, Philip Zisman, Wellington V. Cardoso, Ronald H. Goldstein, Raphael Breuer
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2012)
Article
Biochemistry & Molecular Biology
Aliete Langsdorf, Valerie Schumacher, Xiaofeng Shi, Thanh Tran, Joseph Zaia, Sanjay Jain, Mary Taglienti, Jordan A. Kreidberg, Alan Fine, Xingbin Ai
Article
Biochemistry & Molecular Biology
Zhihua Jiang, Nan Yu, Pingping Kuang, Melody Chen, Fengzhi Shao, Gregory Martin, David H. K. Chui, Wellington V. Cardoso, Xingbin Ai, Jining Lu
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Biochemistry & Molecular Biology
Thanh H. Tran, Xiaofeng Shi, Joseph Zaia, Xingbin Ai
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Immunology
Jason M. Konter, Jennifer L. Parker, Elizabeth Baez, Stephanie Z. Li, Barbara Ranscht, Martin Denzel, Frederic F. Little, Kazuto Nakamura, Noriyuki Ouchi, Alan Fine, Kenneth Walsh, Ross S. Summer
JOURNAL OF IMMUNOLOGY
(2012)
Article
Neurosciences
Oliver R. Braubach, Nobuhiko Miyasaka, Tetsuya Koide, Yoshihiro Yoshihara, Roger P. Croll, Alan Fine
JOURNAL OF NEUROSCIENCE
(2013)
Article
Multidisciplinary Sciences
Jesus Paez-Cortez, Ramaswamy Krishnan, Anneliese Arno, Linh Aven, Sumati Ram-Mohan, Kruti R. Patel, Jining Lu, Oliver D. King, Xingbin Ai, Alan Fine
Article
Multidisciplinary Sciences
Arjun Guha, Michelle Vasconcelos, Yan Cai, Mitsuhiro Yoneda, Anne Hinds, Jun Qian, Guihua Li, Lauren Dickel, Jane E. Johnson, Shioko Kimura, Jinjin Guo, Jill McMahon, Andrew P. McMahon, Wellington V. Cardoso
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2012)
Article
Respiratory System
Sara E. Manoli, Lacey A. Smith, Carrie A. Vyhlidal, Chang Hyeok An, Yolanda Porrata, Wellington V. Cardoso, Rebecca M. Baron, Kathleen J. Haley
RESPIRATORY RESEARCH
(2012)
Article
Respiratory System
Edward E. Morrisey, Wellington Cardoso, Robert H. Lane, Marlene Rabinovitch, Steven H. Abman, Xingbin Ai, Kurt H. Albertine, Richard D. Bland, Harold A. Chapman, William Checkley, Jonathan A. Epstein, Christopher R. Kintner, Maya Kumar, Parviz Minoo, Thomas J. Mariani, Donald M. McDonald, Yoh-suke Mukouyama, Lawrence S. Prince, Jeff Reese, Janet Rossant, Wei Shi, Xin Sun, Zena Werb, Jeffrey A. Whitsett, Dorothy Gail, Carol J. Blaisdell, Qing S. Lin
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2013)