Article
Multidisciplinary Sciences
Shyam K. Akula, Jack H. Marciano, Youngshin Lim, David Exposito-Alonso, Norma K. Hylton, Grace H. Hwang, Jennifer E. Neil, Nicole Dominado, Rosie K. Bunton-Stasyshyn, Janet H. T. Song, Maya Talukdar, Aloisia Schmid, Lydia Teboul, Alisa Mo, Taehwan Shin, Benjamin Finander, Samantha G. Beck, Rebecca C. Yeh, Aoi Otani, Xuyu Qian, Ellen M. DeGennaro, Fowzan S. Alkuraya, Sateesh Maddirevula, Gregory D. Cascino, Caterina Giannini, Lindsay C. Undiagnosed Diseases Network, Lindsay C. Burrage, Jill A. Rosenfield, Shamika Ketkar, Gary D. Clark, Carlos Bacino, Richard A. Lewis, Rosalind A. Segal, J. Fernando Bazan, Kelly A. Smith, Jeffrey A. Golden, Ginam Cho, Christopher A. Walsh
Summary: This study reveals the role of TMEM161B in regulating Sonic hedgehog signaling and cerebral cortical gyration during embryonic development. Mutations in TMEM161B are associated with multiple abnormalities including polymicrogyria. TMEM161B is involved in primary ciliary structure and its dysfunction may contribute to ciliary-related phenotypes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Yibin Pan, Jiena Zhou, Weidan Zhang, Lili Yan, Meifei Lu, Yongdong Dai, Hanjing Zhou, Songying Zhang, Jianhua Yang
Summary: The study found up-regulation of SHH and accumulation of SQSTM1/P62 in epithelial ovarian cancer. Cyp induced autophagy through the PI3K/AKT signaling pathway, and low-dose Cyp and chloroquine (CQ) significantly promoted the migratory ability of SKOV3 cells. The findings suggest that inhibition of the SHH pathway and autophagy may be a potential and effective therapy for the treatment of ovarian cancer.
Article
Pharmacology & Pharmacy
Fanping Wang, Xiaoyu Huang, Yanwei Sun, Zhixin Li, Ruili Sun, Tiesuo Zhao, Mingyong Wang, Chunxia Yan, Peijun Liu
Summary: This study investigated the effects of sulforaphane (SFN), the main ingredient in broccoli, on the proliferation of leukemia stem-like cells in acute myeloid leukemia cells. The results showed that SFN inhibited the proliferation of leukemia stem-like cells and regulated the stem characteristic of leukemia cells. Furthermore, SFN was found to negatively modulate proliferation of these cells by affecting the Sonic Hedgehog pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Oncology
Hongping Wang, Qun Lai, Dayong Wang, Jian Pei, Baogang Tian, Yunhe Gao, Zhaoguo Gao, Xiang Xu
Summary: This study reviewed the role of the HH signaling pathway in the occurrence and progression of GBM, as well as the effectiveness of drugs that target the HH pathway. The findings highlight the key role of HH signaling in the occurrence, development, and treatment of GBM.
Article
Biology
Andrew M. Hamilton, Olga A. Balashova, Laura N. Borodinsky
Summary: Research indicates that Hedgehog (Hh) signaling may be a useful target for driving regeneration, and non-canonical mechanisms of Hh signaling are necessary for spinal cord and muscle regeneration.
Review
Biochemistry & Molecular Biology
Steven A. Hill, Marissa Fu, A. Denise R. Garcia
Summary: Astrocytes are complex cells performing essential functions in the nervous system. The Sonic hedgehog (Shh) signaling pathway plays a crucial role in regulating the molecular identity and functional properties of astrocytes, and is active in specific subpopulations of these cells throughout the brain.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Friederike Hantel, Huaize Liu, Lisa Fechtner, Herbert Neuhaus, Jie Ding, Danilo Arlt, Peter Walentek, Pablo Villavicencio-Lorini, Christoph Gerhardt, Thomas Hollemann, Thorsten Pfirrmann
Summary: Cilia play an important role in embryonic development, and the GID complex is involved in primary cilia-dependent signal transduction and protein homeostasis. GID subunits may be candidate genes for human ciliopathies associated with defects in Hedgehog signaling.
JOURNAL OF CELL SCIENCE
(2022)
Article
Cell Biology
Po-Hsuan Su, Rui-Lan Huang, Hung-Cheng Lai, Lin-Yu Chen, Yu-Chun Weng, Chih-Chien Wang, Chia-Chun Wu
Summary: NKX6-1 expression is associated with poor prognosis and malignant potential in LMS, enhancing tumor cell aggressiveness in vitro and promoting tumor growth in vivo. Overexpression and knockdown of NKX6-1 affect stem cell transcription factors and signaling pathways, including the NOTCH and Sonic hedgehog pathways. Inhibition of the SHH pathway may be a potential therapeutic strategy for LMS patients with high expression of NKX6-1.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Developmental Biology
Adam W. Olson, Vien Le, Jinhui Wang, Alex Hiroto, Won Kyung Kim, Dong-Hoon Lee, Joseph Aldahl, Xiwei Wu, Minhyung Kim, Gerald R. Cunha, Sungyong You, Zijie Sun
Summary: The study demonstrates that stromal androgen receptor (AR) action is crucial for prostate development, and selective deletion of stromal AR expression in prepubescent Gli1-expressing cells disrupts androgen signaling-initiated stromal-epithelial paracrine interactions, leading to growth retardation and developmental defects in pubertal prostate epithelia. Aberrant shh-signaling activation and altered differentiation fates of prostatic epithelial cells are identified as key mechanisms affected by stromal AR deletion.
Article
Multidisciplinary Sciences
Sangwoo Shim, Raman Goyal, Alexios A. Panoutsopoulos, Olga A. Balashova, David Lee, Laura N. Borodinsky
Summary: The balance between neural stem cell proliferation and neuronal differentiation is crucial for the development of the nervous system. We found that Sonic hedgehog (Shh) enhances Ca2+ activity at the cilia of developing Xenopus laevis embryos, which promotes neuronal differentiation and inhibits proliferative signaling. These findings provide potential targets for the treatment of brain tumors and neurodevelopmental disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Pingping Yu, Li Wang, Fanren Tang, Shuang Guo, Hongyan Liao, Cengceng Fan, Qin Yang
Summary: Resveratrol pretreatment promotes neurorestoration of ischemic cerebral injury through mediation of the Sonic Hedgehog signaling pathway, enhancing proliferation of neural stem cells.
Review
Pharmacology & Pharmacy
Vikas Daggubati, David R. Raleigh, Navdar Sever
Summary: This article discusses the role of the Hedgehog (Hh) family of lipid-modified signaling proteins in embryonic tissue patterning and postembryonic tissue homeostasis, as well as the involvement of dysregulated Hh signaling in familial and sporadic cancers. It also explores the binding and modulation of SMO activity by endogenous cholesterol and oxidized cholesterol derivatives. The article proposes models of sterol regulation of SMO and discusses the potential utility of steroidal SMO ligands or inhibitors of enzymes involved in sterol metabolism as cancer therapeutics.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
W. Wang, J. Qiu, P. Qu, H. Chen, J. Lan, H. Chen, L. Li, M. Gu
Summary: The study found that dysregulation of the ROC1-SUFU-GLI2 axis plays an important role in bladder cancer progression. ROC1 overexpression promotes bladder cancer cell growth by targeting SUFU for ubiquitin-dependent degradation, resulting in activation of the SHH pathway. Knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity and cancer cell growth.
CANCER CELL INTERNATIONAL
(2021)
Article
Developmental Biology
Wenguang Yin, Andreas Liontos, Janine Koepke, Maroua Ghoul, Luciana Mazzocchi, Xinyuan Liu, Chunyan Lu, Haoyu Wu, Athanasios Fysikopoulos, Alexandros Sountoulidis, Werner Seeger, Clemens Ruppert, Andreas Gunther, Didier Y. R. Stainier, Christos Samakovlis
Summary: The tracheal epithelium is a crucial element in pulmonary diseases, and its understanding of cell proliferation and differentiation is limited. The Hedgehog (HH) signaling pathway plays a role in communication between epithelial and mesenchymal cells in the lung, affecting stromal cell proliferation, differentiation, and epithelial signaling. This study discovered an autocrine HH signaling function in airway epithelial cells, with its inhibition leading to defects in cell proliferation and differentiation. Additionally, HH function is mediated by transcriptional activation, as inhibition of HH signaling downregulates cell type-specific transcription factor genes in both mouse trachea and human airway epithelial cells. These findings provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.
Article
Biology
Xiaodong Li, Patrick J. Gordon, John A. Gaynes, Alexandra W. Fuller, Randy Ringuette, Clayton P. Santiago, Valerie Wallace, Seth Blackshaw, Pulin Li, Edward M. Levine
Summary: This article investigates how the tissue-specific transcription factor Lhx2 regulates Sonic Hedgehog (Shh) signaling at multiple levels during early retinal neurogenesis. Lhx2 acts cell autonomously to control the expression of pathway genes required for efficient activation and maintenance of Shh signaling in retinal progenitor cells. The study also identifies Cdon and Gas1 as candidate direct targets of Lhx2 that mediate pathway activation. Through these interactions, Lhx2 establishes the competence for Shh signaling in retinal progenitors and promotes early retinal neurogenesis.
Article
Biochemistry & Molecular Biology
Jianhua Xiong, Hiroyuki Kawagishi, Ye Yan, Jie Liu, Quinn S. Wells, Lia R. Edmunds, Maria M. Fergusson, Zu-Xi Yu, Ilsa I. Rovira, Evan L. Brittain, Michael J. Wolfgang, Michael J. Jurczak, Joshua P. Fessel, Toren Finkel
Article
Physiology
Xiaoguang Guo, Toshihide Kashihara, Tsutomu Nakada, Toshifumi Aoyama, Mitsuhiko Yamada
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Yosuke Yamada, Makoto Harada, Koji Hashimoto, Ran Guo, Takero Nakajima, Toshihide Kashihara, Mitsuhiko Yamada, Toshifumi Aoyama, Yuji Kamijo
GLYCOCONJUGATE JOURNAL
(2019)
Article
Peripheral Vascular Disease
Ran Guo, Xiao Hu, Yosuke Yamada, Makoto Harada, Takero Nakajima, Toshihide Kashihara, Mitsuhiko Yamada, Toshifumi Aoyama, Yuji Kamijo
HYPERTENSION RESEARCH
(2019)
Article
Pharmacology & Pharmacy
Hao Zhang, Toshihide Kashihara, Tsutomu Nakada, Satoshi Tanaka, Kumiko Ishida, Satoshi Fuseya, Hiroyuki Kawagishi, Kenkichi Kiyosawa, Mikito Kawamata, Mitsuhiko Yamada
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2019)
Article
Multidisciplinary Sciences
Hajime Ichimura, Shin Kadota, Toshihide Kashihara, Mitsuhiko Yamada, Kuniaki Ito, Hideki Kobayashi, Yuki Tanaka, Naoko Shiba, Shinichiro Chuma, Shugo Tohyama, Tatsuichiro Seto, Kenji Okada, Koichiro Kuwahara, Yuji Shiba
SCIENTIFIC REPORTS
(2020)
Article
Endocrinology & Metabolism
Nanqi Cui, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Hisaka Kawate, Megumu Tanaka, Masaaki Tanaka, Yangxuan Wei, Shinji Kakihara, Yunlu Zhao, Kohsuke Aruga, Hiroyuki Kawagishi, Tsutomu Nakada, Mitsuhiko Yamada, Takayuki Shindo
Summary: The AM-RAMP2 system is crucial for early adaptation to cardiovascular stress in the heart, regulating cardiac mitochondria function. On the other hand, the AM-RAMP3 system plays a critical role in long-term adaptation by regulating lymphatic vessels in the heart. Both systems are essential for maintaining cardiovascular homeostasis against stress.
Article
Biochemistry & Molecular Biology
Ryan Houston, Shiori Sekine, Michael J. Calderon, Fayaz Seifuddin, Guanghui Wang, Hiroyuki Kawagishi, Daniela A. Malide, Yuesheng Li, Marjan Gucek, Mehdi Pirooznia, Alissa J. Nelson, Matthew P. Stokes, Jacob Stewart-Ornstein, Steven J. Mullett, Stacy G. Wendell, Simon C. Watkins, Toren Finkel, Yusuke Sekine
Article
Cardiac & Cardiovascular Systems
Hideaki Inazumi, Koichiro Kuwahara, Yasuaki Nakagawa, Yoshihiro Kuwabara, Takuro Numaga-Tomita, Toshihide Kashihara, Tsutomu Nakada, Nagomi Kurebayashi, Miku Oya, Miki Nonaka, Masami Sugihara, Hideyuki Kinoshita, Kenji Moriuchi, Hiromu Yanagisawa, Toshio Nishikimi, Hirohiko Motoki, Mitsuhiko Yamada, Sachio Morimoto, Kinya Otsu, Richard M. Mortensen, Kazuwa Nakao, Takeshi Kimura
Summary: NRSF is a transcriptional repressor that suppresses the reactivation of fetal cardiac gene program and maintains cardiac integrity. This study reveals that NRSF regulates ventricular function by controlling the expression of G alpha(o) gene, and excessive expression of G alpha(o) leads to cardiac dysfunction. Additionally, G alpha(o) plays a critical role in cardiac Ca2+ homeostasis and systolic function.
CIRCULATION RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Hiroyuki Kawagishi, Tsutomu Nakada, Takuro Numaga-Tomita, Maite Larranaga, Ang Guo, Long-Sheng Song, Mitsuhiko Yamada
Summary: Although the regulatory mechanisms and physiological importance of cardiomyocyte proliferation in the early postnatal period have not been clarified, this study found that pharmacological and genetic depletion of gp130 in preweaning mice resulted in significant impairment of cardiomyocyte proliferation, thinning of the myocardium, and systolic dysfunction of the left ventricle by perturbing JAK/STAT3 signaling. Therefore, the IL-6/gp130/JAK/STAT3 axis is crucial for the postnatal functional development of the left ventricle.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Mitsuhiko Yamada, Hiroyuki Kawagishi, Shin Kadota, Yuji Shiba, Sachio Morimoto
Article
Cardiac & Cardiovascular Systems
Toshihide Kashihara, Hiroyuki Kawagishi, Tsutomu Nakada, Takuro Numaga-Tomita, Shin Kadota, Elena E. Wolf, Cheng-Kun Du, Yuji Shiba, Sachio Morimoto, Mitsuhiko Yamada
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2020)
Meeting Abstract
Cardiac & Cardiovascular Systems
H. Inazumi, K. Kuwahara, Y. Kuwabara, Y. Nakagawa, H. Kinoshita, K. Moriuchi, H. Yanagisawa, T. Nishikimi, M. Oya, M. Yamada, T. Kashihara, N. Kurebayashi, M. Sugihara, K. Nakao, T. Kimura
EUROPEAN HEART JOURNAL
(2019)
Article
Cardiac & Cardiovascular Systems
Andrew B. Harvey, Renelyn A. Woltes, Raymond N. Deepe, Hannah G. Tarolli, Jenna R. Drummond, Allison Trouten, Auva Zandi, Jeremy L. Barth, Rupak Mukherjee, Martin J. Romeo, Silvia G. Vaena, Ge Tao, Robin Muise-Helmericks, Paula S. Ramos, Russell A. Norris, Andy Wessels
Summary: This study highlights the importance of SOX9 in the regulation of epicardial cell invasion and emphasizes the role of EPDCs in regulating atrioventricular valve development and homeostasis. It also reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Review
Cardiac & Cardiovascular Systems
MariaSanta C. Mangione, Jinhua Wen, Dian J. Cao
Summary: mTOR, a mechanistic target of rapamycin, is an evolutionarily conserved pathway that plays a fundamental role in nutrient sensing, growth, metabolism, lifespan, and aging. Recent studies have highlighted the regulatory role of mTOR in innate immune responses and its involvement in the pathogenesis of cardiovascular diseases, especially in acute inflammation and atherosclerotic cardiovascular disease. This review also discusses mTOR's role in trained immunity, immune senescence, and clonal hematopoiesis, as well as its architecture and regulatory complexes.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Junlin Li, Yajun Gong, Yiren Wang, Huihui Huang, Huan Du, Lianying Cheng, Cui Ma, Yongxiang Cai, Hukui Han, Jianhong Tao, Gang Li, Panke Cheng
Summary: Myocardial ischemia-reperfusion injury is closely related to the final infarct size in acute myocardial infarction. Regulatory T cells play an important role in the inflammatory response after AMI, but different subtypes of Tregs have different effects on the injury.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Yuxin Chu, Yutao Hua, Lihao He, Jin He, Yunxi Chen, Jing Yang, Ismail Mahmoud, Fanfang Zeng, Xiaochang Zeng, Gloria A. Benavides, Victor M. Darley-Usmar, Martin E. Young, Scott W. Ballinger, Sumanth D. Prabhu, Cheng Zhang, Min Xie
Summary: This study demonstrates that administering beta-hydroxybutyrate (beta-OHB) at the time of reperfusion can reduce infarct size and preserve cardiac function by activating autophagy and preserving mitochondrial homeostasis, potentially through mTOR inhibition.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)