Editorial Material
Cell Biology
Philippe de Medina, Julio Bunay, Marc Poirot, Michel Record, Sandrine Silvente-Poirot
Summary: Normal cells secrete small extracellular vesicles (sEV) that play a beneficial role in tissue integrity and immune response, while cancer cells secrete sEV that inhibit immune defenses and promote tumor progression. This study explores the potential of reprogramming tumor sEV to function more like normal sEV through the use of dendrogenin A (DDA), which induced tumor cell differentiation and growth inhibition at low doses. The study also discovered a novel pathway involving the DDA-NR1H2 complex that enhances the secretion of sEV with immune and anticancer properties. These findings may lead to the development of new therapeutic strategies against pro-tumor exosomes.
Article
Multidisciplinary Sciences
Xiufei Cao, Wei Fang, Xueshan Li, Xiuneng Wang, Kangsen Mai, Qinghui Ai
Summary: LDLR plays a crucial role in hepatic triglyceride accumulation in fish, and its expression is directly or indirectly regulated by SREBP2. SREBP2 can directly activate LDLR transcription and indirectly regulate LDLR through increasing the transcription of lncRNA LDLR-AS. Mechanism analysis revealed that LDLR-AS acts as an RNA scaffold to stabilize LDLR mRNA.
Article
Clinical Neurology
Giulia Birolini, Gianluca Verlengia, Francesca Talpo, Claudia Maniezzi, Lorena Zentilin, Mauro Giacca, Paola Conforti, Chiara Cordiglieri, Claudio Caccia, Valerio Leoni, Franco Taroni, Gerardo Biella, Michele Simonato, Elena Cattaneo, Marta Valenza
Summary: This study highlights the importance of glial SREBP2 in the pathogenesis of Huntington's disease and demonstrates that AAV-based delivery of SREBP2 to astrocytes can counteract key features of the disease.
Article
Biology
Xin Zhou, Seula Shin, Chenxi He, Qiang Zhang, Matthew N. Rasband, Jiangong Ren, Congxin Dai, Rocio Zorrilla-Veloz, Takashi Shingu, Liang Yuan, Yunfei Wang, Yiwen Chen, Fei Lan, Jian Hu
Summary: This study reveals the crucial role of Qki in controlling cholesterol biosynthesis in the central nervous system, which is essential for myelinogenesis. Depletion of Qki results in reduced cholesterol concentration in the brain, impairing proper myelin assembly.
Article
Plant Sciences
Chijun Hou, Xinyue Jiang, Wenjuan Sheng, Yuling Zhang, Qianbei Lin, Shihan Hong, Jiale Zhao, Ting Wang, Xiaohan Ye
Summary: In this study, the researchers investigated the effect of Xinmaikang (XMK) tablets on atherosclerosis (AS) and explored the underlying mechanism. They found that XMK improved serum lipids, reduced plaque area, inhibited inflammatory cytokines, and improved inflammation through the SREBP2-mediated NLRP3/ASC/Caspase-1 signaling pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Alberto Canfran-Duque, Noemi Rotllan, Xinbo Zhang, Irene Andres-Blasco, Bonne M. Thompson, Jonathan Sun, Nathan L. Price, Marta Fernandez-Fuertes, Joseph W. Fowler, Diego Gomez-Coronado, William C. Sessa, Chiara Giannarelli, Robert J. Schneider, George Tellides, Jeffrey G. McDonald, Carlos Fernandez-Hernando, Yajaira Suarez
Summary: The accumulation of 25-hydroxycholesterol (25-HC) in human coronary atherosclerotic lesions accelerates atherosclerosis progression and promotes plaque instability through autocrine and paracrine actions. Macrophage-derived 25-HC intensifies the inflammatory response of lipid-loaded macrophages and inhibits smooth muscle cell migration within the plaque. These effects are independent of 25-HC-mediated modulation of transcriptional activity.
Article
Biotechnology & Applied Microbiology
Bai-Mei Zhuang, Dan-Dan Cao, Tian-Xi Li, Xiao-Feng Liu, Min-Min Lyu, Si-Dong Wang, Xin-Yuan Cui, Li Wang, Xiao-Lin Chen, Xiao-Li Lin, Cheuk-Lun Lee, Philip C. N. Chiu, William S. B. Yeung, Yuan-Qing Yao
Summary: Our study provides a single-cell atlas for trophoblast organoids (TOs) and explores their applications in extravillous trophoblast (EVT) differentiation and communication with decidual natural killer (dNK) cells. We identified multiple distinct trophoblast states and dNK subpopulations, and found a close resemblance between TO/EVT-TO and human placenta. Transcription factors were found to be essential for controlling EVT differentiation, and ligand-receptor complexes related to cytokines, immunomodulation, and angiogenesis were predicted in dNK-EVT-TO co-cultures. Furthermore, we found that dNK cells can exert effects on EVT causing functionally important expression changes.
Article
Biochemistry & Molecular Biology
Ye Tian, Yuelei Zhao, Wensai Yu, Sherif Melak, Yingfang Niu, Wei Wei, Lifan Zhang, Jie Chen
Summary: This study investigated the role of ACAT2 in intramuscular adipocyte differentiation and found that individuals with high intramuscular fat had low levels of ACAT2, while individuals with low intramuscular fat had high levels of ACAT2. The results suggest that ACAT2 functions as a negative regulator of intramuscular adipocyte differentiation through the regulation of ppary, cebpc, srebp2, and ldlr signaling pathways involved in cholesterol metabolism.
Article
Nutrition & Dietetics
Yunhua Zhang, Ziming Zhu, Lijun Sun, Wenzhen Yin, Yuan Liang, Hong Chen, Yanghui Bi, Wenbo Zhai, Yue Yin, Weizhen Zhang
Summary: This study found that single-nucleotide polymorphisms in G protein-coupled receptor 180 (GPR180) are associated with hypertriglyceridemia. Knocking down hepatic GPR180 resulted in decreased triglyceride and cholesterol contents, improved hepatic lipid deposition, and reduced adiposity. It also downregulated transcription factors and their target genes related to lipid metabolism. Therefore, GPR180 may be a potential drug target for the intervention of obesity and liver steatosis.
Article
Biochemistry & Molecular Biology
Liu-Ya Tang, Marie Spezia, Ting Chen, Jee-Hye Shin, Feng Wang, Frank Stappenbeck, Andres M. Lebensohn, Farhad Parhami, Ying E. Zhang
Summary: The study revealed that oxysterols Oxy186 and Oxy210 can inhibit proliferation of NSCLC cells, with Oxy186 exhibiting potent inhibition of tumor growth. The mechanism of action involves inhibiting the WNT/beta-catenin signaling pathway.
CELL AND BIOSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Mikko Karpale, Aki Juhani Karajamaki, Outi Kummu, Helena Gylling, Tuulia Hyotylainen, Matej Oresic, Ari Tolonen, Heidi Hautajarvi, Markku J. Savolainen, Mika Ala-Korpela, Janne Hukkanen, Jukka Hakkola
Summary: This study investigated the role of PXR receptor in regulating atherogenic lipid levels in humans and found that PXR activation induces cholesterol synthesis, leading to elevated LDL and total cholesterol. The PXR-SREBP2 pathway was identified as a novel regulator of cholesterol and PCSK9 synthesis, providing a molecular mechanism for drug- and chemical-induced hypercholesterolemia.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Marcy Martin, Jiao Zhang, Yifei Miao, Ming He, Jian Kang, Hsi-Yuan Huang, Chih-Hung Chou, Tse-Shun Huang, Hsiao-Chin Hong, Shu-Han Su, Simon S. Wong, Rebecca L. Harper, Lingli Wang, Rakesh Bhattacharjee, Hsien-Da Huang, Zhen Bouman Chen, Atul Malhotra, Marlene Rabinovitch, James S. Hagood, John Y-J Shyy
Summary: This study revealed the critical role of SREBP2 in idiopathic pulmonary fibrosis, by inducing phenotypic modifications in endothelial cells, leading to the upregulation of various gene pathways and mesenchymal genes expression. The findings suggest that SREBP2 may exacerbate pulmonary fibrosis in both rodent models and human patients with IPF, indicating its potential as a therapeutic target for this progressive lung disease.
Article
Multidisciplinary Sciences
Lara Bideyan, Wenxin Fan, Karolina Elibieta Kaczor-Urbanowicz, Christina Priest, David Casero, Peter Tontonoz
Summary: Liver X receptors play crucial roles in hepatic metabolism, affecting genes involved in fatty acid metabolism and broad sets of hepatic transcription factors. Loss of LXR binding in liver can lead to increased expression of certain genes and decreased expression of others.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Rebekka Bauer, Sofie Patrizia Meyer, Rebecca Raue, Megan A. Palmer, Vanesa Maria Guerrero Ruiz, Giulia Cardamone, Silvia Roesser, Milou Heffels, Fabian Roesmann, Alexander Wilhelm, Dieter Luetjohann, Kathi Zarnack, Dominik Christian Fuhrmann, Marek Widera, Tobias Schmid, Bernhard Bruene
Summary: Hypoxia reduces cholesterol biosynthesis and activates SREBP2, while increasing interferon-stimulated gene (ISG) expression in monocytes. Intracellular cholesterol distribution plays a critical role in enhancing hypoxic expression of chemokine ISGs. Hypoxia sensitizes TLR4 signaling to enhance chemokine ISG induction following SARS-CoV-2 infection in monocytes, potentially contributing to severe inflammatory responses in COVID-19.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Runqiu Xu, Qi Liu, Xiaoxue Ma, Jingbo Hou
Summary: The study demonstrates that irisin suppresses PCSK9 expression through the AMPK-SREBP2 pathway and ameliorates ox-LDL-induced endothelial cells inflammation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Kazuhiro Kajiwara, Ofer Beharier, Choon-Peng Chng, Julie P. Goff, Yingshi Ouyang, Claudette M. St Croix, Changjin Huang, Valerian E. Kagan, K. Jimmy Hsia, Yoel Sadovsky
Summary: Ferroptosis is a regulated form of cell death characterized by oxidative damage to phospholipids, resulting in membrane macro-blebbing and vesiculation. Trophoblasts are particularly susceptible to ferroptosis, and the presence of membrane macro-blebbing serves as a marker for this process.
JOURNAL OF CELL SCIENCE
(2022)
Review
Developmental Biology
Ofer Beharier, Kazuhiro Kajiwara, Yoel Sadovsky
Summary: Programmed cell death is essential in controlling tissue development, organismal physiology, and disease. Ferroptosis, a newly identified form of cell death, has been linked to placental physiology and injury and may play a critical role in placental disorders.
Article
Microbiology
Yingshi Ouyang, Tarique Bagalkot, Wendy Fitzgerald, Elena Sadovsky, Tianjiao Chu, Ana Martinez-Marchal, Miguel Brieno-Enriquez, Emily J. Su, Leonid Margolis, Alexander Sorkin, Yoel Sadovsky
Summary: Research has shown that the main entry factors for SARS-CoV-2 are expressed in human placental trophoblasts, but not in other placental villous cells. The placental defense against SARS-CoV-2 infection likely involves post-entry processing mechanisms.
Article
Endocrinology & Metabolism
Fernanda Alvarado-Flores, Tomoko Kaneko-Tarui, William Beyer, Jacqueline Katz, Tianjiao Chu, Patrick Catalano, Yoel Sadovsky, Marie-France Hivert, Perrie O'Tierney-Ginn
Summary: Maternal insulin resistance during late pregnancy is associated with the expression of placental miRNA-3940-3p, suggesting a potential regulatory role of this miRNA in modulating maternal insulin resistance.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Multidisciplinary Sciences
Mirella Mourad, Taylor Jacob, Elena Sadovsky, Shai Bejerano, Glicella Salazar-De Simone, Tarique Rajasaheb Bagalkot, Jason Zucker, Michael T. Yin, Jennifer Y. Chang, Lihong Liu, Larisa Debelenko, Carrie J. Shawber, Morgan Firestein, Yingshi Ouyang, Cynthia Gyamfi-Bannerman, Anna Penn, Alexander Sorkin, Ronald Wapner, Yoel Sadovsky
Summary: The severity of COVID-19 in pregnant women is associated with the processing of SARS-CoV-2 in the placenta and antiviral pathways, suggesting a role for these proteins in the placental response to SARS-CoV-2.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Tianjiao Chu, Jean-Francois Mouillet, Zhishen Cao, Oren Barak, Yingshi Ouyang, Yoel Sadovsky
Summary: Researchers investigated the interactions between non-coding RNAs and protein-coding RNAs in the human placenta, identifying key biological processes during trophoblast differentiation that may be impaired in common gestational diseases like fetal growth restriction and preeclampsia. This study enhances understanding of the mechanisms involved in trophoblast differentiation and the potential implications for gestational health.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Obstetrics & Gynecology
Fernanda Alvarado-Flores, Anastasia Savelyeva, Tianjiao Chu, Yoel Sadovsky, Ndidiamaka Amutah-Onukagha, Perrie O'Tierney-Ginn
Summary: Non-Hispanic Black (NHB) individuals have a higher risk of maternal mortality and their neonates are more likely to be preterm and small for gestational age compared to Non-Hispanic White (NHW) individuals, potentially due to structural racism. The placental miRNA expression profile differs between NHB and NHW individuals, with some miRNAs associated with cellular stress response pathways. The lower expression of miR-192-5p in the placenta of NHB individuals is positively correlated with neonatal adiposity, suggesting its sensitivity to structural racism and potential impact on fetal growth.
REPRODUCTIVE SCIENCES
(2022)
Article
Obstetrics & Gynecology
Juliana S. Powell, Robin E. Gandley, Emily Lackner, Andrea Dolinish, Yingshi Ouyang, Robert W. Powers, Adrian E. Morelli, Carl A. Hubel, Yoel Sadovsky
Summary: Preeclampsia is a pregnancy syndrome that can threaten the survival of both mother and baby. Research suggests that sEVs from pregnant women with preeclampsia play a significant role in the regulation of arterial tone.
PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH
(2022)
Review
Immunology
Adrian E. Morelli, Yoel Sadovsky
Summary: This article explores the mechanisms underlying maternal tolerance of the semi- or fully-allogeneic fetus, with a focus on the role of extracellular vesicles (EVs) in immune modulation, providing a new perspective on immune suppression and activation during pregnancy.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Developmental Biology
Changjin Huang, Hui Li, Juliana S. Powell, Yingshi Ouyang, Stacy G. Wendell, Subra Suresh, K. Jimmy Hsia, Yoel Sadovsky, David Quinn
Summary: In this study, the researchers characterized membrane viscosities of different types of extracellular vesicles (EVs) collected from primary human trophoblasts using fluorescence lifetime imaging microscopy (FLIM). They found that EV types derived from the same cell type exhibit different membrane viscosities. The membrane viscosity of microvesicles was shown to faithfully reflect hypoxic injury of the human trophoblasts.
Article
Microbiology
Mary Frances Keith, Kathyayini Parlakoti Gopalakrishna, Venkata Hemanjani Bhavana, Gideon Hayden Hillebrand, Jordan Lynn Elder, Christina Joann Megli, Yoel Sadovsky, Thomas Alexander Hooven
Summary: Intrauterine infection caused by group B Streptococcus (GBS) is a common cause of miscarriage and preterm birth. This study investigated the role of nitric oxide (NO) production and GBS survival mechanisms in host-pathogen interactions during GBS chorioamnionitis. It was found that placental NOS expression increased, NO inhibited GBS growth, and GBS activated stress pathways in response to NO exposure.
Article
Multidisciplinary Sciences
Jinxin Zhang, Chuyi Chen, Ryan Becker, Joseph Rufo, Shujie Yang, John Mai, Peiran Zhang, Yuyang Gu, Zeyu Wang, Zhehan Ma, Jianping Xia, Nanjing Hao, Zhenhua Tian, David T. W. Wong, Yoel Sadovsky, Luke P. Lee, Tony Jun Huang
Summary: This study presents a technique called ANSWER, which allows for rapid and high-purity fractionation of sEV subpopulations from biofluids. The technique utilizes excitation resonance to generate pillar-like acoustic fields, enabling precise separation of particles in a size-selective manner without the need for sample preprocessing or complex nanofabrication methods.
Article
Medicine, Research & Experimental
Jennifer Guerrero-Santoro, Mayumi Morizane, Soo-Young Oh, Takuya Mishima, Julie P. Goff, Ibrahim Bildirici, Elena Sadovsky, Yingshi Ouyang, Vladimir A. Tyurin, Yulia Y. Tyurina, Valerian E. Kagan, Yoel Sadovsky
Summary: In eutherians, the placenta is crucial for the uptake, storage, and metabolism of lipids. However, the regulation of placental lipid droplet lipolysis remains unknown. This study found that the absence of CGI58, not PNPLA2, significantly increased placental lipid droplet accumulation. Additionally, PNPLA9 contributed to lipolysis in human placental trophoblasts.
Article
Developmental Biology
Oren Barak, Tyler Lovelace, Tianjiao Chu, Zhishen Cao, Elena Sadovsky, Jean-Francois Mouillet, Yingshi Ouyang, Panayiotis Benos, Yoel Sadovsky
Summary: This study examines the relationship between trophoblast injury and placental dysfunction syndromes. By studying the mRNA of primary human trophoblasts exposed to injuries in vitro, distinct trophoblast injury patterns were found in placental biopsies from women with fetal growth restriction and a hypertensive disorder. The RNAseq data provide insights into the contribution of trophoblast injuries to placental dysfunction.
Article
Developmental Biology
Elena Sadovsky, Tianjiao Chu, Oren Barak, Yoel Sadovsky, Yingshi Ouyang
Summary: This study examined the expression of opioid receptors (OPRs) in villous trophoblasts and the impact of opioids on placental transcriptomics. The findings suggest that the expression of OPRs and opioid RNA targets in trophoblasts is influenced by cell differentiation, indicating differential susceptibility of villous trophoblasts to the effects of opioids.