Article
Biochemistry & Molecular Biology
Jinhua Wei, Dongdong Liu, Tong Xu, Limeng Zhu, Siming Jiao, Xubing Yuan, Zhuo A. Wang, Jianjun Li, Yuguang Du
Summary: This study utilized vascular glycocalyx on chips to evaluate the changes of glycocalyx and its constituent glycans in High Glucose (HG) induced HUVECs. The results showed up-regulation of hyaluronan (HA) and down-regulation of heparan sulfate (HS). The metabolic enzymes analysis demonstrated a decrease in the ratio of synthetic/degradative enzymes for HA and an increase in that for HS. Omics analysis revealed an increase in the synthesis substrates for both glycans. The differential changes of HA and HS were also confirmed in vessel slides from db/db mice.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Prashant Jain, Chethan D. Shanthamurthy, Shani Leviatan Ben-Arye, Sharon Yehuda, Sharvani S. Nandikol, Hirekodathakallu Thulasiram, Vered Padler-Karavani, Raghavendra Kikkeri
Summary: A potential heparan sulfate (HS) ligand was discovered to target several growth factors using specific HS tetrasaccharide ligands. One tetrasaccharide ligand showed strong binding with the VEGF(165) growth factor, and in vitro experiments demonstrated the therapeutic potential of these synthetic HS ligands by inhibiting vascular endothelial cell proliferation, migration, and angiogenesis in the presence of VEGF(165) and the specific tetrasaccharides.
CHEMICAL COMMUNICATIONS
(2021)
Article
Neurosciences
Fangfang Zhao, Liyuan Zhong, Yumin Luo
Summary: The blood-brain barrier is a complex neurovascular unit that protects neurons and maintains stability of the central nervous system, with endothelial glycocalyx playing a critical role in its structure and functions. Damage to glycocalyx can lead to dysfunction and neurological diseases, highlighting the importance of research in providing theoretical basis for diagnosis and treatment.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Lakshmi N. R. Thota, Joaquin E. Lopez Rosales, Ivan Placencia, Evgeny A. Zemskov, Paola Tonino, Ashley N. Michael, Stephen M. Black, Andreia Z. Chignalia
Summary: The endothelial glycocalyx is an important signaling layer involved in cellular homeostasis. Its diverse composition and relative contributions of its constituents to overall function are still not well understood. The deletion of glypican 1, a glycocalyx component, results in a modified glycocalyx without affecting baseline lung endothelial function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Linda M. Hiebert
Summary: Diabetes is a complex disease that affects millions of people worldwide, and the role of proteoglycans, particularly heparan sulfate proteoglycans (HSPGs), in its pathogenesis has recently gained attention. HSPGs play crucial roles in various physiological processes, and their modification in diabetes can lead to complications in different tissues and organs. Understanding the role of HSPGs in diabetes may help develop new treatments and preventive measures for this condition.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Article
Biochemistry & Molecular Biology
Sohyun Moon, Ying-Tao Zhao
Summary: The study systematically analyzed the spatial, temporal, and cell-type-specific expression of genes encoding HS biosynthesis enzymes and HSPG core proteins, providing a valuable resource for the research community in the field of heparan sulfate.
Review
Biochemistry & Molecular Biology
Anthony J. J. Hayes, James Melrose
Summary: Heparan sulfate is a complex glycosaminoglycan that plays important roles in various biological processes through interactions with extracellular ligands and cellular receptors. Its chain lengths and sequences can vary, providing structural diversity. Heparan sulfate has regulatory properties in tissue development, wound healing, immune regulation, inflammation, and tumor development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Amrita Basu, Neil G. Patel, Elijah D. Nicholson, Ryan J. Weiss
Summary: Glycosaminoglycans (GAGs) are long polysaccharides found on the cell surface and extracellular matrix of animal cells, and play important roles in cellular processes and diseases. GAGs are complex molecules with extensive structural and functional heterogeneity, and their biosynthesis is a non-template driven process involving a group of enzymes. Due to their key roles in cell homeostasis and disease, targeting the assembly and function of GAGs is of great interest as a therapeutic approach.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Cell Biology
Marwa Mahmoud, Limary Cancel, John M. Tarbell
Summary: Matrix stiffness affects the expression of GCX in endothelial cells, making it unsuitable for specific cell types to study the endothelial glycocalyx on stiff matrices such as glass or plastic.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Tanya Waseem, Madiha Ahmed, Tausif Ahmed Rajput, Mustafeez Mujtaba Babar
Summary: Diabetes mellitus leads to metabolic derangements and organ damage, partially due to glycosaminoglycan (GAG) damage in the basement membrane. GAGs are polysaccharides with repeating disaccharide units and play a significant role in cellular processes. The destruction of extracellular matrix can result in various diseases in organs. GAG-based therapeutic agents are being evaluated for managing diabetic complications.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Medicine, Research & Experimental
Stefan Lennard Krautschneider, Fabian M. Troschel, Eduardo Vadillo, Hans Theodor Eich, Martin Goette, Nancy Adriana Espinoza-Sanchez, Burkhard Greve
Summary: This study aimed to investigate the interplay between heparan sulfate (HS) degradation and radiation response in triple-negative breast cancer (TNBC) cells. The results showed significantly increased radioresistance and cell migration after HS degradation. Furthermore, the expression and activation of certain signaling pathway molecules were altered after HS degradation, impacting the radiation resistance of TNBC cells.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Virology
Ghadah A. Karasneh, Divya Kapoor, Navya Bellamkonda, Chandrashekhar D. Patil, Deepak Shukla
Summary: The increased levels of HPSE can reduce syncytial plaque formation and promote viral egress and release. Transiently enhanced expression of HPSE does not affect HSV-1 entry into cells but facilitates extracellular release of mature virions.
Article
Hematology
Kaori Oshima, Samantha King, Sarah A. McMurtry, Eric P. Schmidt
Summary: The importance of endothelial glycocalyx and its in vivo manifestation, the endothelial surface layer, in vascular homeostasis is increasingly recognized. During sepsis, shedding of endothelial HSPGs through sheddases like heparanase and matrix metalloproteinases can lead to vascular dysfunction. Degradation of glycocalyx releases HSPG fragments into circulation, shaping the systemic consequences of sepsis.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Article
Physiology
Cassandra J. Field, Alexis M. Perez, Taryn Samet, Victoria Ricles, M. Kathryn Iovine, Linda J. Lowe-Krentz
Summary: Tmem184a plays a critical role in the proper formation of blood vessels in zebrafish embryos. It acts synergistically with Vegfr2b to modulate angiogenesis and affects endothelial cell proliferation and VE-cadherin expression.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Sang Hoon Kim, Fiona L. Kearns, Mia A. Rosenfeld, Lorenzo Casalino, Micah J. Papanikolas, Carlos Simmerling, Rommie E. Amaro, Ronit Freeman
Summary: GlycoGrip is a lateral flow assay developed based on the role of cell-surface glycoproteins as coreceptors for pathogens, allowing for the detection of SARS-CoV-2 and its variants. By utilizing glycopolymers and antibody-gold nanoparticle conjugates, it achieves sensitive and rapid virus detection. Through computational optimization, the test strips have been fine-tuned to selectively detect the virus in biofluids.
ACS CENTRAL SCIENCE
(2022)
Letter
Nutrition & Dietetics
David S. Ludwig, Louis J. Aronne, Arne Astrup, Rafael de Cabo, Lewis C. Cantley, Mark Friedman, Steven B. Heymsfield, James D. Johnson, Janet C. King, Ronald M. Krauss, Daniel E. Lieberman, Gary Taubes, Jeff S. Volek, Eric C. Westman, Walter C. Willett, William S. Yancy, Cara B. Ebbeling
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2022)
Article
Cardiac & Cardiovascular Systems
Ying Wang, Hua Gao, Fudi Wang, Zhongde Ye, Michal Mokry, Adam W. Turner, Jianqin Ye, Simon Koplev, Lingfeng Luo, Tom Alsaigh, Shaunak S. Adkar, Maria Elishaev, Xiangyu Gao, Lars Maegdefessel, Johan L. M. Bjorkegren, Gerard Pasterkamp, Clint L. Miller, Elsie G. Ross, Nicholas J. Leeper
Summary: This study reveals that vascular smooth muscle cells (SMCs) undergo dedifferentiation and activation of pro-inflammatory pathways during the development of atherosclerosis. ATF3, a transcription factor, is identified as an upstream regulator of this transition. ATF3 represses the transition of SMCs towards a subset of cells that promote vascular inflammation by activating the complement cascade. The expression of ATF3 is negatively correlated with complement component C3, and genetic variations that reduce ATF3 expression are associated with an increased risk for atherosclerosis.
CARDIOVASCULAR RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Haoning Howard Cen, Bahira Hussein, Jose Diego Botezelli, Su Wang, Jiashuo Aaron Zhang, Nilou Noursadeghi, Niels Jessen, Brian Rodrigues, James A. Timmons, James D. Johnson
Summary: Hyperinsulinemia, often considered as a compensatory response to insulin resistance, may actually contribute to insulin resistance. The molecular mechanisms underlying this cyclic process are poorly understood. This study found a reliable negative correlation between fasting insulin and INSR mRNA in skeletal muscle. Through cell culture experiments, it was demonstrated that elevated insulin levels attenuated AKT and ERK signaling in muscle cells. RNA-sequencing analysis revealed changes in gene expression related to insulin receptor signaling, FOXO signaling, and glucose metabolism pathways. Hyperinsulinemia led to reduced Insr gene expression and decreased surface INSR protein. SIN3A was identified as a negative regulator of Insr mRNA. These findings provide insights into the mechanisms of hyperinsulinemia-induced insulin resistance in muscle.
Article
Endocrinology & Metabolism
Sandra Postic, Srdjan Sarikas, Johannes Pfabe, Viljem Pohorec, Lidija Krizancic Bombek, Nastja Sluga, Masa Skelin Klemen, Jurij Dolensek, Dean Koro, Andraz Stonzer, Carmella Evans-Molina, James D. Johnson, Marjan Slak Rupnik
Summary: Physiological glucose or ryanodine stimulation of 13 cell collectives generates a large number of [Ca2+]c events, which can be rapidly assessed with our newly developed automatic image segmentation and [Ca2+]c event identification pipeline. The event durations segregate into three reproducible modes produced by a progressive temporal summation. Using pharmacological tools, we show that activation of ryanodine intracellular Ca2+ receptors is both sufficient and necessary for glucose-dependent [Ca2+]c oscillations in 13 cell collectives.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Cell Biology
Connie L. K. Leung, Subashini Karunakaran, Michael G. Atser, Leyla Innala, Xiaoke Hu, Victor Viau, James D. Johnson, Susanne M. Clee
Summary: Genetic factors play a role in obesity, but their effects are generally small. Studying animal models can provide insights into the genetic regulation of obesity. This study identified novel genes, Pdk1 and Itga6, that may modulate obesity, lipid metabolism, insulin secretion, and glucose homeostasis.
PHYSIOLOGICAL GENOMICS
(2023)
Article
Cardiac & Cardiovascular Systems
Chae Syng Lee, Yajie Zhai, Rui Shang, Trevor Wong, Aurora J. Mattison, Haoning Howard Cen, James D. Johnson, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
Summary: The study found that flow-induced mechanical forces can increase the release of heparanase from endothelial cells, affecting cardiac metabolism. The release of heparanase is mediated by activation of purinergic receptors and protein kinase D, and is augmented in diabetes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Endocrinology & Metabolism
George P. Brownrigg, Yi Han Xia, Chieh Min Jamie Chu, Su Wang, Charlotte Chao, Jiashuo Aaron Zhang, Sos Skovso, Evgeniy Panzhinskiy, Xiaoke Hu, James D. Johnson, Elizabeth J. Rideout
Summary: This study aims to investigate the crucial role of pancreatic beta cells in maintaining glucose homeostasis and the impact of sex differences on this process. By comparing the gene expression and function of beta cells in males and females, we found that female patients have more reliable insulin secretion and higher resilience to endoplasmic reticulum stress.
MOLECULAR METABOLISM
(2023)
Article
Endocrinology & Metabolism
Austin J. Taylor, Evgeniy Panzhinskiy, Paul C. Orban, Francis C. Lynn, David F. Schaeffer, James D. Johnson, Janel L. Kopp, C. Bruce Verchere
Summary: Loss of IAPP signaling may not increase the risk of pancreatic cancer in individuals with diabetes.
MOLECULAR METABOLISM
(2022)
Article
Endocrinology & Metabolism
Ben Vanderkruk, Nina Maeshima, Daniel J. Pasula, Meilin An, Cassandra L. McDonald, Priya Suresh, Dan S. Luciani, Francis C. Lynn, Brad G. Hoffman
Summary: This study finds that H3K4 methylation is essential for the maintenance of mature beta cell function, and the redistribution of H3K4me3 is closely related to gene expression changes implicated in diabetes pathology.
Review
Physiology
Liam G. Hall, John P. Thyfault, James D. Johnson
Summary: Exercise and regular physical activity are beneficial for preventing and managing metabolic diseases, while exercise cessation can lead to metabolic derangements. This article reviews the impact of exercise and exercise cessation on β-cell function, with a focus on glucose-stimulated insulin secretion (GSIS). It also explores potential mechanisms by which β-cells adapt to exercise and highlights areas for future research.
JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Sos Skovso, Peter Overby, Jasmine Memar-Zadeh, Jason T. C. Lee, Jenny C. C. Yang, Iryna Shanina, Vaibhav Sidarala, Elena Levi-D'Ancona, Jie Zhu, Scott A. Soleimanpour, Marc S. Horwitz, James D. Johnson
Summary: The study confirmed the protective effects of Cre in preventing diabetes development in NOD mice, and suggested the possibility that Cre itself may have additional protective effects.
Meeting Abstract
Endocrinology & Metabolism
P. Overby, S. Provenzano, G. Sun, N. Nahirney, J. Kolic, S. Skovso, J. D. Johnson
Meeting Abstract
Endocrinology & Metabolism
A. Zhang, K. H. Chu, Y. Xia, T. Ruiter, J. Yang, J. Lin, N. Chen, D. F. Schaeffer, J. L. Kopp, J. D. Johnson
Meeting Abstract
Endocrinology & Metabolism
H. H. Cen, V. R. Richard, Y. H. Xia, S. Skovso, J. D. Botezelli, X. Hu, J. Collier, R. P. Zahedi, C. H. Borchers, J. D. Johnson
Meeting Abstract
Endocrinology & Metabolism
J. C. M. Chu, H. Modi, S. Skovso, C. Ellis, N. A. J. Krentz, Y. B. Zhao, H. Cen, N. Noursadeghi, E. Panzhinskiy, Y. Xia, S. Xuan, M. O. Huising, T. J. Kieffer, F. C. Lynn, J. D. Johnson