Article
Orthopedics
Yulei Liu, Xiang-Hua Deng, Xueying Zhang, Ting Cong, Daoyun Chen, Arielle Jordan Hall, Liang Ying, Scott A. Rodeo
Summary: The Indian hedgehog signaling pathway plays an important role in the development and healing process of supraspinatus tendon tendinopathy in a mouse shoulder impingement model. With the relief of impingement, tendon pathology gradually improves, while the signaling pathway and its downstream mediator GLI1 continue to increase.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Jian Yi Chai, Vaisnevee Sugumar, Mohammed Abdullah Alshawsh, Won Fen Wong, Aditya Arya, Pei Pei Chong, Chung Yeng Looi
Summary: The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved in mammals and plays crucial roles in cancer initiation and progression. GLI transcription factors are regulated by both SMO-dependent and SMO-independent mechanisms, with dysregulation leading to tumorigenesis in various cancers. Understanding the complex interplay between GLI and signaling elements could inspire new therapeutic breakthroughs for Hh-GLI-dependent cancers.
Review
Oncology
Meng Zhang, Lijuan Gao, Yiping Ye, Xiaoyu Li
Summary: GLI inhibitors have great potential in various cancer treatments, effectively inhibiting the self-renewal of cancer stem cells and addressing issues such as tumor growth, metastasis, and drug resistance.
INVESTIGATIONAL NEW DRUGS
(2022)
Review
Oncology
Ashley N. Sigafoos, Brooke D. Paradise, Martin E. Fernandez-Zapico
Summary: The Hedgehog/GLI pathway is crucial during development and often dysregulated in diseases like cancer. Activation in cancer is typically through a non-canonical, ligand-independent mechanism. This pathway involves a series of components that work together to repress or activate signaling cascades.
Article
Medicine, Research & Experimental
Chao Tang, Ximei Wu, Qianlei Ren, Minli Yao, Shouying Xu, Ziyi Yan
Summary: This study uncovers a novel mechanism controlling Hh signaling through the activation of Rac1 and subsequent translocation of Gli. Rac1 activation affects KIF3A phosphorylation and IFT88 stability, thereby disrupting SuFu-Gli complex formation and releasing Gli for nuclear translocation.
Article
Gastroenterology & Hepatology
Lu Zhuang, Yao Yao, Lisi Peng, Fang Cui, Cui Chen, Yang Zhang, Liqi Sun, Qihong Yu, Kun Lin
Summary: This study reveals that GSH2 is overexpressed in pancreatic cancer and silencing it can inhibit cell proliferation, migration, invasion, and increase sensitivity to gemcitabine. Silencing GSH2 alleviates gemcitabine resistance by activating the SHH/GLI1 pathway in pancreatic cancer, suggesting that targeting GSH2 could be a novel therapeutic strategy for PDAC.
DIGESTIVE DISEASES AND SCIENCES
(2022)
Article
Oncology
Su Hyun Lee, Ji Sun Lee, Jae Hyeon Park, Sungpil Yoon, Kwang Youl Lee, Hyung Sik Kim
Summary: The study reveals that GLI1 plays a role in promoting cell proliferation and glycolysis in TNBC. Inhibiting GLI1 expression can suppress the growth and proliferation of breast cancer cells, as well as decrease their glycolytic rates, thereby inhibiting tumor progression.
Article
Oncology
Weijiang Wu, Hanqing Yang, Zhutao Wang, Zhijian Zhang, Xiaodong Lu, Wenjing Yang, Xiayue Xu, Yinuo Jiang, Yan Li, Xin Fan, Qixiang Shao
Summary: The study confirms that OPN is highly expressed in human PDAC tissues and cell lines, and Gli1 is associated with OPN expression in human PDAC, regulating OPN production in BxPC-3 cells through a noncanonical pathway. Knockdown of Gli1 reduces proliferation, migration, and invasion of BxPC-3 cells while increasing apoptosis.
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
(2021)
Review
Immunology
Yazhen Su, Hao Xing, Jie Kang, Linkun Bai, Liyun Zhang
Summary: The Hedgehog (Hh) signaling pathway plays a crucial role in rheumatic diseases and has the potential to be a therapeutic target.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Erik P. Beadle, Natalie E. Bennett, Julie A. Rhoades
Summary: Liposarcomas are rare soft tissue malignancies with varying clinical prognosis. Well-differentiated and dedifferentiated liposarcomas commonly occur in extremities and the retroperitoneal cavity. Surgical resection and post-operative monitoring are effective treatments, but recurrence is common and chemotherapy may be necessary. Hedgehog signaling is upregulated in dedifferentiated liposarcomas and is associated with reduced immune cell infiltration and increased extracellular matrix protein expression.
Article
Multidisciplinary Sciences
Marzena Swiderska-Syn, Julia Mir-Pedrol, Alexander Oles, Olga Schleuger, April D. Salvador, Sean M. Greiner, Cara Seward, Fan Yang, Benjamin R. Babcock, Chen Shen, Daniel T. Wynn, Avencia Sanchez-Mejias, Timothy R. Gershon, Vanesa Martin, Heather J. McCrea, Kathryn G. Lindsey, Carsten Krieg, Jezabel Rodriguez-Blanco
Summary: Single-cell transcriptomic analysis of medulloblastoma revealed that vismodegib treatment increased Sox2-expressing astrocyte-like cells. These Sox2(+) cells relied on Sonic Hedgehog (SHH) signaling, with MYC-dependent activation downstream of Smo. GLI inhibitors depleted resistant Sox2(+) cells, reduced their engraftment ability, and increased symptom-free survival.
Article
Oncology
Somanath Kundu, Mohan S. Nandhu, Sharon L. Longo, John A. Longo, Shawn Rai, Lawrence S. Chin, Timothy E. Richardson, Mariano S. Viapiano
Summary: DLG5 is upregulated in malignant gliomas and promotes invasion, viability, and self-renewal of glioblastoma stem cells. It regulates Sonic Hedgehog (Shh) signaling, making DLG5-deficient cells insensitive to Shh ligand, and its loss increases the proteasomal degradation of Gli1, leading to tumor stem cell sensitization. These findings reveal a novel and pro-tumoral role for DLG5 in glioblastoma, distinct from its proposed tumor-suppressor role in other solid tumors.
Article
Oncology
Elisabeth Peer, Sophie Karoline Aichberger, Filip Vilotic, Wolfgang Gruber, Thomas Parigger, Sandra Grund-Groeschke, Dominik Patrick Elmer, Florian Rathje, Andrea Ramspacher, Mirko Zaja, Susanne Michel, Svetlana Hamm, Fritz Aberger
Summary: Inhibition of CSNK1D represents a novel therapeutic approach for both SMO inhibitor-sensitive and -resistant tumors, suppressing oncogenic HH-GLI signaling and reducing malignant properties of tumor-initiating cells. This study provides a basis for the development of efficient CSNK1D inhibitors as a potential therapy for HH-GLI-associated cancers.
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)
Review
Cell Biology
Chamey Suchors, James Kim
Summary: The Hedgehog signaling pathway is crucial for development and tissue regeneration, and its dysregulation has been linked to cancer. Our understanding of this pathway in tumorigenesis has significantly advanced over the past few decades. The pathway can have both tumor-suppressive and oncogenic functions, and noncanonical activation of GLI transcription factors has been observed in certain types of tumors.
Editorial Material
Cell Biology
Liliana Schaefer
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Timon Eckes, Sammy Patyna, Alexander Koch, Anke Oftring, Stefan Gauer, Nicholas Obermueller, Stephanie Schwalm, Liliana Schaefer, Jerold Chun, Hermann-Josef Groene, Josef Pfeilschifter
Summary: This study found that S1P(5) deficiency can improve tubular damage and tubulointerstitial fibrosis in a mouse model of adenine-induced nephropathy, and reduce inflammation. Therefore, targeting S1P(5) may be a promising therapeutic target for kidney diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Fabian Schramm, Liliana Schaefer, Malgorzata Wygrecka
Summary: This review article provides an overview of the ErbB receptor-ligand system and its importance in developmental and physiological processes. It focuses on the role of ErbB receptors and their ligands in maladaptive remodeling of lung tissue, specifically in idiopathic pulmonary fibrosis (IPF). The article discusses the pathways and cellular processes contributing to miscommunication between epithelial and mesenchymal cells in IPF, and reviews in vivo studies on the efficacy of ErbB signaling inhibitors in lung injury models. Additionally, it discusses lessons learned from clinical applications of ErbB1 signaling inhibitors in cancer to inform clinical trials in IPF.
Editorial Material
Cell Biology
Elie El Agha, Malgorzata Wygrecka
Article
Cell Biology
Vahid Kheirollahi, Ali Khadim, Georgios Kiliaris, Martina Korfei, Margarida Maria Barroso, Ioannis Alexopoulos, Ana Ivonne Vazquez-Armendariz, Malgorzata Wygrecka, Clemens Ruppert, Andreas Guenther, Werner Seeger, Susanne Herold, Elie El Agha
Summary: This study provides a comprehensive transcriptional profile of IGF signaling components in mice during embryonic lung development, bleomycin-induced pulmonary fibrosis, and human IPF lung explants. The findings suggest that Igf1 is upregulated in the lung mesenchyme during late gestation, while Igf1r is downregulated. In lung fibrosis, IGF1 is upregulated while IGF1R is downregulated, and several IGF binding proteins are upregulated. Treatment of IPF lung fibroblasts with recombinant IGF1 leads to myogenic differentiation.
Editorial Material
Cell Biology
Eric Delpire, Thomas J. Hawke, Mythreye Karthikeyan, Wei Kong, Alexander Nystroem, Shizuka Uchida, Liliana Schaefer
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Review
Cell Biology
Malgorzata Wygrecka, Ioannis Alexopoulos, Daniel P. Potaczek, Liliana Schaefer
Summary: ApoA-I plays an important role in reverse cholesterol transport and also possesses anti-inflammatory and antioxidative functions. Dysfunctional apoA-I or its low abundance can lead to the formation of foam cells in alveolar macrophages. Increased numbers of foam cells have been observed in the lungs of mice exposed to certain substances and in patients with lung fibrosis. Understanding the role of apoA-I in lung fibrosis provides potential avenues for therapeutic development.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wei Peng, Artem Kepsch, Till O. Kracht, Hiba Hasan, Rukmali Wijayarathna, Eva Wahle, Christiane Pleuger, Sudhanshu Bhushan, Stefan Guenther, A. Christine Kauerhof, Ana Planinic, Daniela Fietz, Hans-Christian Schuppe, Malgorzata Wygrecka, Kate L. Loveland, Davor Jezek, Andreas Meinhardt, Mark P. Hedger, Monika Fijak
Summary: Experimental autoimmune-orchitis (EAO), a rodent model of chronic testicular inflammation and fibrosis, replicates pathogenic changes seen in some cases of human spermatogenic disturbances. CCR2 and activin A promote fibrosis during testicular inflammation by regulating macrophage function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Agnes Sauer, Benjamin Seeliger, Katharina Jandl, Lasti Erfinanda, Jochen Wilhelm, Ioannis Alexopoulos, Nelli Baal, Anna Birnhuber, Sascha David, Tobias Welte, Guillermo Barreto, Ulrich Gaertner, Grazyna Kwapiszewska, Werner Seeger, Wolfgang M. Kuebler, Liliana Schaefer, Malgorzata Wygrecka
Summary: This study reveals the association between the severity of community-acquired pneumonia (CAP) and acute respiratory distress syndrome (ARDS) with hyaluronan (HA) levels and size in plasma. Increased HA levels are correlated with disease severity, inflammation, endothelial cell activation, and basement membrane destruction, and are associated with increased 28-day mortality. The study also shows that pneumolysin (PLY), a toxin secreted by Streptococcus pneumoniae, induces HA shedding from human pulmonary microvascular endothelial cells (HPMVEC) through reactive oxygen species (ROS) production.
Editorial Material
Cell Biology
Liliana Schaefer, Sandrine V. Pierre
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Review
Cell Biology
Sarah Miethe, Daniel P. Potaczek, Stanislawa Bazan-Socha, Melanie Bachl, Liliana Schaefer, Malgorzata Wygrecka, Holger Garn
Summary: Extracellular vesicles (EVs) have gained attention for their role in intercellular signaling, particularly in the connection between adipose tissue (AT) and the lung in diseases such as obesity-associated asthma and lung cancer-associated cachexia. Studies have shown both pathogenic and protective effects of EVs in these diseases, with AT-derived EVs playing a potential therapeutic role. Further research is needed to better understand the role of EVs in disease development and organ interconnectivity.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Immunology
Katharina Jandl, Johannes Lorenz Berg, Anna Birnhuber, Elisabeth Fliesser, Izabela Borek, Benjamin Seeliger, Sascha David, Julius J. Schmidt, Gregor Gorkiewicz, Martin Zacharias, Tobias Welte, Horst Olschewski, Akos Heinemann, Malgorzata Wygrecka, Grazyna Kwapiszewska
Summary: Immune cell recruitment, endothelial cell barrier disruption, and platelet activation are common in lung injuries like COVID-19-induced ARDS. In this study, we investigated the role of endostatin, a bioactive fragment of the basement membrane protein collagen XVIII alpha 1, on cellular functions associated with ARDS. Our results showed that endostatin enhanced neutrophil and platelet activity, as well as induced microvascular barrier disruption.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Critical Care Medicine
Malgorzata Wygrecka, Lukasz Wujak, Philipp Markart, Djuro Kosanovic, Holger C. Mueller-Redetzky, Martin Witzenrath, Ingrid Henneke, Ralph T. Schermuly, Werner Seeger, Liliana Schaefer, Grazyna Kwapiszewska, Leigh M. Marsh, Nelli Baal, Holger Hackstein, Steven de Maat, Coen Maas
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)