Review
Immunology
Melanie Rose, Marie Duhamel, Franck Rodet, Michel Salzet
Summary: Proprotein convertases (PCs) are a family of serine proteases that process cellular pro-proteins and play a crucial role in cellular homeostasis. Specifically, in lymphoid organs, PCs such as Furin are involved in immune response regulation, with knock-out of Furin in T cells associated with increased inflammatory cytokine secretion and autoantibody production. Additionally, PCs like Furin and PC1/3 have been shown to regulate the innate and adaptive immune responses, suggesting their potential as therapeutic targets in oncoimmune therapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Tamadher A. Alghamdi, Nicole A. J. Krentz, Nancy Smith, Aliya F. Spigelman, Varsha Rajesh, Alokkumar Jha, Mourad Ferdaoussi, Kunimasa Suzuki, Jing Yang, Jocelyn E. Manning Fox, Han Sun, Zijie Sun, Anna L. Gloyn, Patrick E. MacDonald
Summary: The Zmiz1 gene in beta cells is essential for maintaining normal glucose homeostasis. Genetic variations at the ZMIZ1 locus may affect the risk of type 2 diabetes by reducing the expansion of beta cell mass and the ability to maintain a mature beta cell state under metabolic stress.
MOLECULAR METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Ilaria Coppola, Bas Brouwers, Sandra Meulemans, Bruno Ramos-Molina, John W. M. Creemers
Summary: FURIN cleaves the insulin receptor non-redundantly in beta cells, while redundantly in liver. The study demonstrated that the insulin receptor in beta cells plays a limited role in glucose homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Cheng Zhang, Hong-Ming Ma, Shuang-Shu Dong, Na Zhang, Ping He, Meng-Kai Ge, Li Xia, Jian-Xiu Yu, Qiang Xia, Guo-Qiang Chen, Shao-Ming Shen
Summary: PTEN alpha and PTEN beta proteins are cleaved into two fragments by Furin enzyme after secretion into the extracellular space. Although these cleaved fragments cannot enter cells, the purified C-terminal fragment has a tumor-suppressive role in vivo. Therefore, the C-terminal fragment may be a potential exogenous agent for cancer treatment.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Ronit Vogt Sionov, Ronit Ahdut-HaCohen
Summary: Type 1 diabetes is a chronic autoimmune disease characterized by the destruction of insulin-producing beta-cells, leading to impaired glucose homeostasis. Mesenchymal stem cells (MSCs) have been found to support pancreatic islet function and protect islets through various mechanisms, including angiogenesis, immune response suppression, and secretion of growth factors.
Article
Immunology
Zsuzsanna Ortutay, Anna Gronholm, Melina Laitinen, Melinda Keresztes-Andrei, Ismail Hermelo, Marko Pesu
Summary: The proprotein convertase enzyme FURIN plays an important role in maintaining cellular homeostasis by promoting the proteolytic maturation of pro-proteins. In T cells, FURIN is crucial for maintaining immune tolerance and T helper cell polarization. A regulatory region upstream of the Furin gene was identified, and deletion of this region reduced the expression of Furin mRNA in activated mouse T cells and affected the expression of genes associated with IFN gamma regulation in Th1 type cells. The Furin genetic regulatory region specifically promoted IFN gamma secretion by activated T cells, indicating characteristics of a super-enhancer for Th1 cell fate.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Yiming Wu, Jie Shi, Qing Su, Zhen Yang, Li Qin
Summary: This study found that circulating PCSK9 levels were significantly higher in pregnant women with gestational diabetes mellitus (GDM) compared to those with normal glucose tolerance. The levels of PCSK9 were positively correlated with fasting plasma glucose, glycated hemoglobin, total cholesterol, and low-density lipoprotein cholesterol in the GDM group. Logistic regression analysis showed that age and serum PCSK9 levels were independently associated with GDM. The study suggests a potential link between PCSK9 and GDM.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Developmental Biology
Nelson J. Ramirez-Suarez, Helen M. Belalcazar, Maisha Rahman, Meera Trivedi, Leo T. H. Tang, Hannes E. Bullow
Summary: Cellular adhesion is crucial for neural development and is mediated by conserved cell adhesion molecules. In this study, the researchers show that the proprotein convertase KPC-1 regulates the Menorin adhesion complex in PVD dendritic arbors development in Caenorhabditis elegans. The balance between KPC-1 and MNR-1 regulates cell-surface localization of the DMA-1 receptor and the abundance of proteins in the Menorin adhesion complex.
Review
Endocrinology & Metabolism
Manita Shakya, Iris Lindberg
Summary: This review discusses the structure, function, and association with human diseases of kexin-like proprotein convertases, highlighting the limitations and challenges of using mouse models in elucidating disease mechanisms and human diseases.
Article
Biochemistry & Molecular Biology
Delia Susan-Resiga, Emmanuelle Girard, Rachid Essalmani, Anna Roubtsova, Jadwiga Marcinkiewicz, Rabeb M. Derbali, Alexandra Evagelidis, Jae H. Byun, Paul F. Lebeau, Richard C. Austin, Nabil G. Seidah
Summary: ASGR1 plays a crucial role in mediating the endocytosis and lysosomal degradation of desialylated glycoproteins in the liver. It independently targets and degrades LDLR along with PCSK9, without cooperativity between the two. Silencing ASGR1 and PCSK9 may increase LDL uptake by hepatocytes, offering a potential approach to reduce LDL cholesterol levels.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Endocrinology & Metabolism
Eun Young Lee, Jing W. Hughes
Summary: Primary cilia are important organelles on the surfaces of most eukaryotic cells that play a role in development and signaling pathways. Dysfunction of cilia is associated with human developmental and genetic disorders, including obesity and diabetes. This article reviews the expression and function of cilia in pancreatic islet cells and discusses the role of cilia in glucose homeostasis and human diseases.
DIABETES & METABOLISM JOURNAL
(2023)
Review
Chemistry, Multidisciplinary
Weikun Huang, Tongzhi Wu, Cong Xie, Christopher K. Rayner, Craig Priest, Heike Ebendorff-Heidepriem, Jiangbo (Tim) Zhao
Summary: The article discusses the importance of calcium ions in intra- and inter-cellular signaling, particularly in insulin secretion. Various sensors for detecting calcium ions are described, with a focus on emerging approaches and challenges in the field.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Chemistry, Organic
Shanping Ji, Steven H. L. Verhelst
Summary: This article reports a series of novel activity-based probes (ABPs) for targeting the serine protease furin using phosphonate and phosphinate esters as reactive electrophiles. The probes are shown to covalently label furin and exhibit nanomolar potencies, likely due to interactions with different recognition pockets around the active site of furin.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Asmaa M. El-kady, Amal M. Alzahrani, Hayam Elshazly, Eman Abdullah Alshehri, Majed H. Wakid, Hattan S. Gattan, Wafa Abdullah I. Al-Megrin, Mashael S. Alfaifi, Khalil Mohamed, Waheeb Alharbi, Hatem A. Elshabrawy, Salwa S. Younis
Summary: This study aimed to investigate the pancreatic pathological changes in mouse models with acute and chronic toxoplasmosis and their association with Type 1 diabetes mellitus (T1DM). The results showed that toxoplasma infection led to a reduction in the number of pancreatic islet cells, which may be associated with the development of T1DM.
Article
Medicine, Research & Experimental
Waleed El Maleky, Amal M. Mahfoz, Afaf O. Osman, Hekma A. Abd El-Latif
Summary: The study demonstrates that Zamzam water significantly reduces hyperglycemia and oxidative stress induced by STZ, improves impaired renal function, alleviates morphological changes and apoptosis in the kidney. Additionally, Zamzam water markedly elevates insulin levels, with more pronounced effects when combined with gliclazide.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Cell & Tissue Engineering
Valentina Cigliola, Luiza Ghila, Simona Chera, Pedro L. Herrera
Review
Biology
Dietrich Averbeck, Serge Candeias, Sudhir Chandna, Nicolas Foray, Anna A. Friedl, Siamak Haghdoost, Penelope A. Jeggo, Katalin Lumniczky, Francois Paris, Roel Quintens, Laure Sabatier
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2020)
Article
Reproductive Biology
Kai Craenen, Mieke Verslegers, Livine Craeghs, Roel Quintens, Ann Janssen, Amelie Coolkens, Sarah Baatout, Lieve Moons, Mohammed Abderrafi Benotmane
REPRODUCTIVE TOXICOLOGY
(2020)
Article
Endocrinology & Metabolism
Shinsuke Tokumoto, Daisuke Yabe, Hisato Tatsuoka, Ryota Usui, Muhammad Fauzi, Ainur Botagarova, Hisanori Goto, Pedro Luis Herrera, Masahito Ogura, Nobuya Inagaki
Article
Endocrinology & Metabolism
Heeyoung Chae, Robert Augustin, Eva Gatineau, Eric Mayoux, Mohammed Bensellam, Nancy Antoine, Firas Khattab, Bao-Khanh Lai, Davide Brusa, Birgit Stierstorfer, Holger Klein, Bilal Singh, Lucie Ruiz, Michael Pieper, Michael Mark, Pedro L. Herrera, Fiona M. Gribble, Frank Reimann, Anne Wojtusciszyn, Christophe Broca, Nano Rita, Lorenzo Piemonti, Patrick Gilon
MOLECULAR METABOLISM
(2020)
Article
Multidisciplinary Sciences
Geoffrey Gaulier, Quentin Dietschi, Swarnendu Bhattacharyya, Cedric Schmidt, Matteo Montagnese, Adrien Chauvet, Sylvain Hermelin, Florence Chiodini, Luigi Bonacina, Pedro L. Herrera, Ursula Rothlisberger, Ivan Rodriguez, Jean-Pierre Wolf
Summary: Experiments have shown that the initial step of vision involves ultra-fast photoisomerization controlled by shaping the phase of femtosecond laser pulses. The electric signals fired from the retina of living mice in response to light stimulation on a femtosecond time scale were found to be sensitive to manipulation of light excitation. This sensitivity is attributed to interactions with light pulses near conical intersections, involving processes like pump-dump and pump-repump.
Article
Biotechnology & Applied Microbiology
Daniel Oropeza, Valentina Cigliola, Agustin Romero, Simona Chera, Santiago A. Rodriguez-Segui, Pedro L. Herrera
Summary: The research demonstrates that alpha-cells undergo stage-specific transcriptional changes at 5 and 15 days post-beta-cell ablation through diphtheria toxin (DT). At day 5, alpha-cells transiently upregulate genes related to interferon signaling and proliferation, while at day 15 they experience a temporary downregulation of genes involved in insulin receptor, mTOR, and MET signaling, indicating potential novel markers and modulated signaling pathways in alpha-cells following acute beta-cell loss.
Article
Multidisciplinary Sciences
Marta Perez-Frances, Leon van Gurp, Maria Valentina Abate, Valentina Cigliola, Kenichiro Furuyama, Eva Bru-Tari, Daniel Oropeza, Taina Carreaux, Yoshio Fujitani, Fabrizio Thorel, Pedro L. Herrera
Summary: Pancreatic polypeptide (Ppy)-expressing gamma-cells are a rare and heterogeneous cell type in the islets, some of which can produce multiple hormones. In response to beta-cell injury, gamma-cells show adaptive plasticity by engaging in insulin production. Loss of Ppy gene or gamma-cells in mice does not affect weight or glycemia under basal conditions.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Marta Perez-Frances, Maria Valentina Abate, Delphine Baronnier, Philipp E. Scherer, Yoshio Fujitani, Fabrizio Thorel, Pedro L. Herrera
Summary: This study investigates the developmental dynamics of pancreatic islet endocrine cell types using murine models. The researchers find that adult islet cells originate from embryonic hormone-expressing cells and there is no evidence of islet cell differentiation from precursor cells after birth. The study also reveals specific patterns of hormone gene activation and switching during islet morphogenesis.
Article
Oncology
Ellina Macaeva, Kevin Tabury, Arlette Michaux, Ann Janssen, Nicole Averbeck, Marjan Moreels, Winnok H. De Vos, Sarah Baatout, Roel Quintens
Summary: Both particle and photon irradiation induce similar transcriptional pathways, with variations in amplitude and timing. However, specific responses unique to each radiation type were also observed, such as enrichment of immune response gene sets in upregulated genes following heavy ion irradiation. Additionally, gene signatures may serve as a sensitive indicator of individual DNA damage repair capacity.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Leon van Gurp, Leon Fodoulian, Daniel Oropeza, Kenichiro Furuyama, Eva Bru-Tari, Anh Nguyet Vu, John S. Kaddis, Ivan Rodriguez, Fabrizio Thorel, Pedro L. Herrera
Summary: The authors used single-cell transcriptomics meta-analysis to construct gene sets that accurately describe the identity of various human islet cells. These gene sets have proven effective in analyzing cell identity changes and their underlying genetic mechanisms, providing reliable tools for cell therapy and diabetes treatment.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Preksha Bhagchandani, Charles A. Chang, Weichen Zhao, Luiza Ghila, Pedro L. Herrera, Simona Chera, Seung K. Kim
Summary: This study introduces a new model of experimental diabetes, the B6 RIP-DTR mouse, which can efficiently induce diabetes and be used for islet transplantation. The model has reliable diabetes induction and the rejection response of transplanted islets can be monitored through blood glucose and histology. Different immune cells can be distinguished using flow cytometry in this model.
SCIENTIFIC REPORTS
(2022)
Review
Biology
Thomas Jaylet, Roel Quintens, Mohamed Abderrafi Benotmane, Jukka Luukkonen, Ignacia Braga Tanaka, Chrystelle Ibanez, Christelle Durand, Magdalini Sachana, Omid Azimzadeh, Christelle Adam-Guillermin, Knut Erik Tollefsen, Olivier Laurent, Karine Audouze, Olivier Armant
Summary: This study organized the current scientific knowledge on microcephaly progression resulting from ionizing radiation exposure and used a machine learning approach to assist in the screening of existing literature. The expert consultation identified crucial biological events and highlighted knowledge gaps. The machine learning approach helped rapidly screen evidence and ensure comprehensive analysis.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2022)
Article
Biology
Kevin Tabury, Mehri Monavarian, Eduardo Listik, Abigail K. Shelton, Alex Seok Choi, Roel Quintens, Rebecca C. Arend, Nadine Hempel, C. Ryan Miller, Balazs Gyorrfy, Karthikeyan Mythreye
Summary: The study demonstrates the role of PVT1, a stress-induced long non-coding RNA, in ovarian cancer growth and metastasis. PVT1 is amplified and overexpressed in ovarian cancer, and its expression is regulated by tumor cells in response to cellular stress. High expression of PVT1 promotes tumor cell survival, growth, and migration, while reducing PVT1 levels effectively inhibits metastatic behavior and tumor cell dissemination. The findings suggest that PVT1 could be a promising therapeutic target to suppress metastasis and chemoresistance in ovarian cancer.
LIFE SCIENCE ALLIANCE
(2022)
Article
Cell & Tissue Engineering
Judith Magenheim, Miguel Angel Maestro, Nadav Sharon, Pedro L. Herrera, L. Charles Murtaugh, Janel Kopp, Maike Sander, Guoqiang Gu, Douglas A. Melton, Jorge Ferrer, Yuval Dor
Summary: Understanding the origin of pancreatic 0 cells is crucial for diabetes regenerative therapies. Previous beliefs that adult pancreatic duct cells serve as endocrine progenitors have been challenged by lineage-tracing experiments. Recent research suggests that adult pancreatic ducts do contain endocrine progenitors, but alternate interpretations argue that these experiments directly label adult islet somatostatin-producing 0 cells, hindering the assessment of duct cell origin for 0 cells. Overall, evidence indicates that the boundaries between endocrine and exocrine lineages are rarely crossed in the adult pancreas.