Article
Chemistry, Medicinal
Oscar Mammoliti, Koen Jansen, Sandy El Bkassiny, Adeline Palisse, Nicolas Triballeau, Denis Bucher, Brigitte Allart, Alex Jaunet, Giovanni Tricarico, Maxim De Wachter, Christel Menet, Javier Blanc, Vatroslav Letfus, Renata Rupcic, Mario Smehil, Tanja Poljak, Beatrice Coornaert, Kathleen Sonck, Inge Duys, Ludovic Waeckel, Lola Lecru, Florence Marsais, Catherine Jagerschmidt, Marielle Auberval, Philippe Pujuguet, Line Oste, Monica Borgonovi, Emanuelle Wakselman, Thierry Christophe, Nicolas Houvenaghel, Mia Jans, Bertrand Heckmann, Laurent Saniere, Reginald Brys
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease, for which current treatments only slow down disease progression, prompting the search for new therapeutic strategies. This study found that S1P2 antagonists could be effective against fibrotic diseases, and developed potentially efficacious compounds through compound mining, structure optimization, and pharmacokinetic improvements based on transporter interactions.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Redona Hafizi, Faik Imeri, Roland H. Wenger, Andrea Huwiler
Summary: The research demonstrates that under normoxic conditions, S1P activates the S1P1 and S1P3 receptors in renal interstitial fibroblasts, promoting Epo production. This finding may have therapeutic implications for conditions like chronic kidney disease that result in anemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Oscar Mammoliti, Adeline Palisse, Caroline Joannesse, Sandy El Bkassiny, Brigitte Allart, Alex Jaunet, Christel Menet, Beatrice Coornaert, Kathleen Sonck, Inge Duys, Philippe Clement-Lacroix, Line Oste, Monica Borgonovi, Emanuelle Wakselman, Thierry Christophe, Nicolas Houvenaghel, Mia Jans, Bertrand Heckmann, Laurent Saniere, Reginald Brys
Summary: Studies suggest that blocking S1P2 receptor signaling could be effective for treating idiopathic pulmonary fibrosis, with only a few antagonists disclosed so far. A chemical enablement strategy led to the discovery of a pyridine series with good antagonist activity, and further optimization identified a compound with potent activity in a phenotypic IL8 release assay and bleomycin-induced model of pulmonary fibrosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Angela Corvino, Ida Cerqua, Alessandra Lo Bianco, Giuseppe Caliendo, Ferdinando Fiorino, Francesco Frecentese, Elisa Magli, Elena Morelli, Elisa Perissutti, Vincenzo Santagada, Giuseppe Cirino, Elisabetta Granato, Fiorentina Roviezzo, Elisa Puliti, Caterina Bernacchioni, Antonio Lavecchia, Chiara Donati, Beatrice Severino
Summary: A new compound acting as an S1P(3) receptor antagonist has been identified, with derivatives synthesized to optimize its activity and selectivity. Further research has shown that compounds selective towards S1P(3) can inhibit skeletal muscle fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Melanie Glueck, Alexander Koch, Robert Brunkhorst, Nerea Ferreiros Bouzas, Sandra Trautmann, Liliana Schaefer, Waltraud Pfeilschifter, Josef Pfeilschifter, Rajkumar Vutukuri
Summary: This study found that d16:1 S1P and CTGF levels are elevated in renal cell carcinoma (RCC), and d16:1 S1P is a more potent agonist for CTGF induction via S1P2 signaling compared to d18:1 and d20:1 S1P. These findings suggest that elevated plasma levels of d16:1 S1P may play a pro-carcinogenic role in the development of RCC via CTGF induction.
Article
Obstetrics & Gynecology
Caterina Bernacchioni, Pasquapina Ciarmela, Valentina Vannuzzi, Stefania Greco, Silvia Vannuccini, Francesca Malentacchi, Pamela Pellegrino, Tommaso Capezzuoli, Flavia Sorbi, Francesca Cencetti, Paola Bruni, Chiara Donati, Felice Petraglia
Summary: The study revealed that S1P signaling is dysregulated in uterine fibroids and involved in activin A-induced fibrosis, presenting new perspectives for the treatment of uterine fibroids.
FERTILITY AND STERILITY
(2021)
Article
Engineering, Environmental
Liang Ou, Peng Zhang, Zhengpeng Huang, Yuxing Cheng, Qianru Miao, Ru Niu, Yuxin Hu, Ying Chen
Summary: Silica is widely used as a chemical raw material, leading to increased exposure and potential hazards to populations, with silicosis being an important representative. The underlying pathogenesis of silicosis is unclear, but studies have shown that the STING signal pathway may play a key role. This study found that silica particles induce the release of double-stranded DNA (dsDNA) to activate the STING signal pathway, leading to inflammation and fibrosis in the lungs.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Cell Biology
Theresa A. Kant, Manja Newe, Luise Winter, Maximilian Hoffmann, Susanne Kaemmerer, Erik Klapproth, Karolina Kuenzel, Mark P. Kuehnel, Lavinia Neubert, Ali El-Armouche, Stephan R. Kunzel
Summary: Pulmonary fibrosis is a chronic progressive disease with limited treatment options, highlighting the need for models to develop effective therapies. Downregulation of PLK2 in human pulmonary fibrosis and the phenotype of PLK2 KO mice suggest a potential genetic predisposition towards pulmonary fibrosis, warranting further investigation into the role of PLK2 in this condition.
Article
Medicine, General & Internal
Alexandria Savage, Cristobal Risquez, Kazunori Gomi, Ryan Schreiner, Alain C. Borczuk, Stefan Worgall, Randi B. Silver
Summary: In addition to traditional activation of resident receptors, exosomes have been found to mediate cell-to-cell communication by delivering specific cargo that modulates recipient cell function. Mast cell exosomes are shown to contribute to excess collagen synthesis, providing a unique paradigm for understanding fibrosis.
FRONTIERS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Gherardo Baudo, Suhong Wu, Matteo Massaro, Haoran Liu, Hyunho Lee, Aijun Zhang, Dale J. Hamilton, Elvin Blanco
Summary: This study aimed to investigate whether improving mitochondrial function can attenuate fibroblast-to-myofibroblast transition (FMT) stimulated by transforming growth factor-beta (TGF-beta). The results demonstrated that administering Dex-TPP-coated mitochondria to TGF-beta-stimulated fibroblasts can inhibit the shift towards glycolysis, reduce reactive oxygen species (ROS) generation, and decrease the expression of FMT markers and extracellular matrix (ECM) proteins, as well as migration and proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Angela K. Peter, Cierra J. Walker, Tova Ceccato, Christa L. Trexler, Christopher D. Ozeroff, Kimberly R. Lugo, Amy R. Perry, Kristi S. Anseth, Leslie A. Leinwand
Summary: The study revealed that chronic beta-AR stimulation in male rat hearts leads to fibrosis, while female rat hearts do not undergo the same response. Additionally, male CFs are more prone to activation compared to female CFs, contributing to increased fibrosis in male rat hearts. The higher beta-AR expression and PKA activation in male CFs may be the underlying mechanism for this sex difference in fibrotic response.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Ophthalmology
M. Victoria Simon, Marcela S. Vera, Paula E. Tenconi, Tamara Soto, Facundo H. Prado Spalm, Camila Torlaschi, Melina Mateos, Nora P. Rotstein
Summary: Retinal pigment epithelium (RPE) cells play a crucial role in maintaining retina homeostasis but also contribute to the development of retina proliferative diseases. Recent studies have revealed that Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) can stimulate migration and inflammation in RPE cells, suggesting their potential as targets for treating these pathologies.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Anissa A. Widjaja, Sivakumar Viswanathan, Dong Jinrui, Brijesh K. Singh, Jessie Tan, Joyce Goh Wei Ting, David Lamb, Shamini G. Shekeran, Benjamin L. George, Sebastian Schafer, David Carling, Eleonora Adami, Stuart A. Cook
Summary: This study elucidates the translation-specific signaling pathways downstream of IL11, intersects immune and metabolic signaling, and reveals unappreciated effects of nintedanib.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Rakhee K. Ramakrishnan, Khuloud Bajbouj, Maha Guimei, Surendra Singh Rawat, Zaina Kalaji, Mahmood Y. Hachim, Bassam Mahboub, Saleh M. Ibrahim, Rifat Hamoudi, Rabih Halwani, Qutayba Hamid
Summary: Subepithelial fibrosis is a characteristic feature of airway remodeling in asthma, and current medications have limited effectiveness in treating fibrosis. The study shows that Bcl10-mediated NF-κB activation is elevated in severe asthmatic bronchial fibroblasts, and is associated with an increased expression of pro-fibrotic cytokines induced by lipopolysaccharide (LPS). Inhibition of the Bcl10-mediated NF-κB pathway shows potential in ameliorating inflammation and fibrosis in severe asthma.
Article
Biology
Salwa Soussi, Lesia Savchenko, Davide Rovina, Jason S. S. Iacovoni, Andrea Gottinger, Maxime Viallettes, Jose-Manuel Pioner, Andrea Farini, Sara Mallia, Martina Rabino, Giulio Pompilio, Angelo Parini, Olivier Lairez, Aoife Gowran, Nathalie Pizzinat
Summary: A study revealed that DMD patients lack the highest molecular weight isoform of dystrophin in their cardiac fibroblasts, leading to altered cell metabolism and mitochondrial function, exacerbating cardiac fibrosis and deterioration of cardiac function.