Article
Multidisciplinary Sciences
Mario C. Benn, Simon A. Pot, Jens Moeller, Tadahiro Yamashita, Charlotte M. Fonta, Gertraud Orend, Philip Kollmannsberger, Viola Vogel
Summary: Controlled tissue growth requires precise control over cell proliferation and differentiation, and the reciprocal feedback between cells and their environment plays a crucial role in this process. Through studying de novo-grown microtissues, we have identified key factors involved in mechanoregulated events that orchestrate the transition from tissue growth to maturation. This knowledge is important for advancing regenerative strategies and combating fibrosis and cancer progression.
Review
Medical Laboratory Technology
Priyanila Magesh, Sanu Thankachan, Thejaswini Venkatesh, Padmanaban S. Suresh
Summary: The fibroblasts in the breast tumor microenvironment are crucial for tumor progression and metastasis, as they provide energy to adjacent cancer cells through metabolic reprogramming and secrete growth factors to promote tumor growth and dissemination. Identifying effective strategies to target the reprogrammed metabolism and communication between fibroblasts and cancer cells could lead to promising anti-cancer therapeutics.
CLINICA CHIMICA ACTA
(2021)
Article
Biology
Mychel R. P. T. Morais, Pinyuan Tian, Craig Lawless, Syed Murtuza-Baker, Louise Hopkinson, Steven Woods, Aleksandr Mironov, David A. Long, Daniel P. Gale, Telma M. T. Zorn, Susan J. Kimber, Roy Zent, Rachel Lennon
Summary: By studying kidney organoids, we have revealed the complex and dynamic nature of basement membrane assembly, and identified its importance in human development and disease.
Article
Biochemistry & Molecular Biology
Tonia K. Tsinman, Xi Jiang, Lin Han, Eiki Koyama, Robert L. Mauck, Nathaniel A. Dyment
Summary: The study tracks the growth of the meniscus in mice from embryonic formation through the first month of growth, revealing that matrix and cellular features defining specific tissue zones are present at birth and further refined with postnatal growth. This work establishes a detailed timeline of spatiotemporal changes at both the cellular and matrix level during meniscus maturation, providing insight into mechanisms of tissue degeneration and regenerative strategies.
Review
Biochemistry & Molecular Biology
Rabab N. Hamzah, Karrer M. Alghazali, Alexandru S. Biris, Robert J. Griffin
Summary: Exosomes are small vesicles produced by various cell types that can transfer cellular components to target cells and affect cell signaling. Recent research suggests that the outcomes of exosome communication depend on the cell type and host cell environment. Key questions remain in cancer research regarding the selectivity of exosome uptake, methods for tracing uptake selectivity, and the impact of donor cell growth environment on cell interaction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Polymer Science
Tingting Yang, Ling Wang, Wen-Hao Wu, Shicheng Wei, Wen-Bin Zhang
Summary: We report an entirely protein-based hydrogel as an artificial ECM that can regulate the growth of embryonic stem cells. A synergy between chemical and physical cross-linking was achieved by SpyTag/SpyCatcher reaction and P zipper association. The stress relaxation behaviors of the hydrogels can be tuned by single-point mutation on a P zipper. Faster relaxation promotes the growth of HeLa tumor spheroids and embryonic stem cells, while mechanical regulation of embryonic stem cells occurs via retention of the cells at the G1 phase. Genetically encoded protein materials show promise as a platform for understanding and controlling complex cell-matrix interactions in 3D cell culture.
Article
Engineering, Biomedical
Evan T. Hoffman, Franziska E. Uhl, Loredana Asarian, Bin Deng, Chloe Becker, Juan J. Uriarte, Isaac Downs, Brad Young, Daniel J. Weiss
Summary: Chronic lung diseases, such as COPD and IPF, exhibit region-specific changes in extracellular matrix (ECM) composition, particularly in collagen and basement-membrane associated proteins. This study compares the ECM composition of whole decellularized lungs and specific anatomical lung regions in non-diseased, COPD, and IPF human lungs. The findings demonstrate distinct ECM signatures in different regions and reveal alterations in ECM composition specific to COPD and IPF, including enrichment of type-III collagen and fibulin in IPF aECM. This study provides methodology for future research and a dataset for identifying novel ECM targets for therapeutics.
Article
Biochemistry & Molecular Biology
Alissa Domaingo, Philipp Jokesch, Alexandra Schweiger, Martha Gschwandtner, Tanja Gerlza, Manuel Koch, Kim S. Midwood, Andreas J. Kungl
Summary: Tenascin-C (TNC) is a complex glycoprotein involved in various physiological processes such as oncogenesis and inflammation. This study investigated the binding of TNC to key chemokines and found a differential chemokine-TNC binding pattern. It was observed that TNC acts as an attenuator in monocyte mobilization and an amplifier in eosinophil mobilization. These effects may be due to TNC impeding the binding of CCL2 to heparan sulfate while reinforcing the binding of CCL26.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Judith Brock, Julia Erhardt, Stephan A. Eisler, Marcel Hoerning
Summary: Cells can sense and adapt to differences in the extracellular microenvironment, including matrix stiffness and protein density. This study investigates the cross-talk between matrix stiffness and protein coating density in regulating the morphology and proliferation dynamics of myocytes.
Article
Engineering, Biomedical
Ruihong Li, Juan Liu, Jie Ma, Xuer Sun, Yi Wang, Jiexin Yan, Qunfang Yu, Jinmei Diao, Chun Yang, Lola M. Reid, Yunfang Wang
Summary: The liver functions depend on interactions between parenchymal cells and the microenvironment, with biological macromolecules in the matrix playing a key role. Rat liver biomatrix scaffold prepared from adult rats is more effective in enhancing hepatic spheroid function. Fibronectin and fibrinogen show potential for improving hepatocyte function, promoting cell aggregation and activating Wnt/beta-catenin pathway.
Article
Chemistry, Physical
Sajjad Naeimipour, Fatemeh Rasti Boroojeni, Robert Selegard, Daniel Aili
Summary: This study presents an enzyme-mediated thiol-based chemistry for the synthesis of carbohydrate-based hydrogels. The method allows for reversible cross-linking and tunable stiffness of the hydrogels by releasing protected thiols through enzymatic reactions. It also enables handling and encapsulation of cells under ambient conditions.
CHEMISTRY OF MATERIALS
(2022)
Article
Engineering, Biomedical
Yixuan Amy Pei, Elmira Mikaeiliagah, Bin Wang, Xiaobing Zhang, Ming Pei
Summary: Recent studies suggest that deposited extracellular matrix (dECM) provides a conducive microenvironment for the proliferation and differentiation of mesenchymal stem cells (MSCs), but the effect of this matrix environment on the lineage differentiation of tissue-specific stem cells remains ambiguous.
MATERIALS TODAY BIO
(2023)
Review
Medicine, General & Internal
Timothy J. Kopper, Xiaoli Yu, Michael W. Graner
Summary: Glioblastomas (GBM) is a devastating disease with poor clinical outcomes. Tumor-derived extracellular vesicles (EVs) impair macrophage function and promote tumor growth. The interaction between macrophages/microglia and gliomas plays a significant role in GBM pathophysiology.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Physiology
Eugenia Papakrivopoulou, Daniyal J. Jafree, Charlotte H. Dean, David A. Long
Summary: This review emphasizes the importance of cell orientation in tissue planes for kidney development and pathology, highlighting the role of planar cell polarity and its proteins in various aspects of kidney organogenesis. Additionally, the relevance of planar cell polarity proteins in inherited human renal diseases, including congenital malformations and polycystic kidney disease, is discussed, as well as the potential for these proteins to influence glomerular diseases and provide new treatment approaches in nephrology.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Hematology
Albert J. Pedroza, Alex R. Dalal, Rohan Shad, Nobu Yokoyama, Ken Nakamura, Paul Cheng, Robert C. Wirka, Olivia Mitchel, Michael Baiocchi, William Hiesinger, Thomas Quertermous, Michael P. Fischbein
Summary: This study provides a detailed characterization of aortic root smooth muscle cells (SMCs) in Marfan syndrome (MFS), revealing the involvement of SMCs derived from both the second heart field (SHF) and neural crest in the formation of aortic root aneurysms. The study also highlights the subtly distinct transcriptional responses between these two lineages and suggests that TWIST1 may play a key role in the enriched collagen synthesis in SHF-derived SMCs in MFS.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Urology & Nephrology
Aude Dorison, Irene Ghobrial, Alison Graham, Thanushi Peiris, Thomas A. A. Forbes, Michael See, Mithun Das, Moin A. A. Saleem, Catherine Quinlan, Kynan T. T. Lawlor, Mirana Ramialison, Sara E. E. Howden, Melissa H. H. Little
Summary: NPHS2 variants are the most common cause of steroid-resistant nephrotic syndrome in children. This study used induced pluripotent stem cell lines to investigate the effects of NPHS2 variants on the expression and subcellular localization of PODOCIN protein, and found that different variants resulted in distinct intracellular localization of PODOCIN, providing insight into the pathobiology of NPHS2 variants.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Pediatrics
Mallory L. Downie, Sanjana Gupta, Melanie M. Y. Chan, Omid Sadeghi-Alavijeh, Jingjing Cao, Rulan S. Parekh, Carmen Bugarin Diz, Agnieszka Bierzynska, Adam P. Levine, Ruth J. Pepper, Horia Stanescu, Moin A. Saleem, Robert Kleta, Detlef Bockenhauer, Ania B. Koziell, Daniel P. Gale
Summary: A genetic risk score can help classify patients with INS presenting in different ways when monogenic causes are excluded.
PEDIATRIC NEPHROLOGY
(2023)
Article
Urology & Nephrology
David Pitcher, Fiona Braddon, Bruce Hendry, Alex Mercer, Kate Osmaston, Moin A. A. Saleem, Retha Steenkamp, Katie Wong, A. Neil Turner, Kaijun Wang, Daniel P. P. Gale, Jonathan Barratt
Summary: Background IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope, and lifetime risks for kidney failure. The study found that almost all patients were at risk of progression to kidney failure within their expected lifetime unless a rate of eGFR loss <= 1 ml/min per 1.73 m(2) per year was maintained.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Cell Biology
Tomasz Kulesza, Marlena Typiak, Patrycja Rachubik, Dorota Rogacka, Irena Audzeyenka, Moin A. Saleem, Agnieszka Piwkowska
Summary: Podocytes play a crucial role in blood filtration, and their proper function depends on efficient insulin responsiveness. Insulin resistance of podocytes, characterized by a reduced sensitivity to insulin, is the earliest mechanism leading to microalbuminuria in metabolic syndrome and diabetic nephropathy. This resistance is mediated by NPP1, an enzyme involved in phosphate homeostasis regulation, which inhibits downstream cellular signaling by binding to the insulin receptor. Hyperglycemic conditions also affect Pit 1, a protein involved in phosphate balance, and our study found an interaction between NPP1 and Pit 1 after stimulation with insulin. Downregulation of the SLC20A1 gene, encoding Pit 1, resulted in insulin resistance in podocytes, indicating that Pit 1 may be a key factor in NPP1-mediated insulin signaling inhibition.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Transplantation
Maarten W. Taal, Bethany Lucas, Paul Roderick, Paul Cockwell, David C. Wheeler, Moin A. Saleem, Simon D. S. Fraser, Rosamonde E. Banks, Tim Johnson, Lorna J. Hale, Uwe Andag, Philipp Skroblin, Michaela Bayerlova, Robert Unwin, Nicolas Vuilleumier, Rodolphe Dusaulcy, Fiona Robertson, Elizabeth Colby, David Pitcher, Fiona Braddon, Melissa Benavente, Elaine Davies, Michael Nation, Philip A. Kalra
Summary: The NURTuRE-CKD cohort is a prospective study that aims to investigate risk factors for adverse outcomes in patients with chronic kidney disease (CKD). The study found that a majority of participants were in high-risk CKD categories, with the primary renal diagnosis being unknown cause. Older participants with lower estimated glomerular filtration rate had higher blood pressure and were less likely to be treated with renin-angiotensin system inhibitors, but were more likely to receive a statin.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Review
Pediatrics
Samantha Hayward, Kevon Parmesar, Moin A. Saleem
Summary: Nephrotic syndrome (NS) is a clinical triad of hypoalbuminemia, high proteinuria, and edema, with various underlying drivers. The existence of circulating factor disease (CFD) as a driver of NS has been proven by disease recurrence in some transplant patients and laboratory work. Several circulating factors, including protease components and immune components, have been proposed and studied. Promising work is being done to assess CFD risk pre-transplantation through the analysis of 'multi-omic' bioinformatic data.
PEDIATRIC NEPHROLOGY
(2023)
Article
Biochemical Research Methods
Carlos Ramirez R. Medina, Ibrahim Ali, Ivona Baricevic-Jones, Aghogho Odudu, Moin A. Saleem, Anthony D. Whetton, Philip A. Kalra, Nophar Geifman
Summary: Using SWATH-MS analysis, we identified 25 biomarkers associated with progression in chronic kidney disease (CKD), which are related to subtype classification and disease-relevant pathways. These findings provide important leads for prevention and treatment of CKD.
CLINICAL PROTEOMICS
(2023)
Article
Biochemistry & Molecular Biology
Maria D. Sanchez-Nino, Maria I. Ceballos, Sol Carriazo, Aranzazu Pintor-Chocano, Ana B. Sanz, Moin A. Saleem, Alberto Ortiz
Summary: The interaction between diabetes and Fabry disease may increase the severity of kidney damage by modulating the Gb3 synthesis pathway and downregulating kidney protective genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Sarah M. Pearsall, Stuart C. Williamson, Sam Humphrey, Ellyn Hughes, Derrick Morgan, Fernando J. Garcia Marques, Griselda Awanis, Rebecca Carroll, Laura Burks, Yan Ting Shue, Abel Bermudez, Kristopher K. Frese, Melanie Galvin, Mathew Carter, Lynsey Priest, Alastair Kerr, Cong Zhou, Trudy G. Oliver, Jonathan D. Humphries, Martin J. Humphries, Fiona Blackhall, Ian G. Cannell, Sharon J. Pitteri, Gregory J. Hannon, Julien Sage, Caroline Dive, Kathryn L. Simpson
Summary: This study investigates the phenotype and molecular mechanisms of vasculogenic mimicry (VM) in small cell lung cancer (SCLC) using circulating tumor cell-derived explant (CDX) models and genetically engineered mouse models (GEMMs). The results show that VM vessels are present in CDX models, GEMMs, and SCLC patient biopsies, and perfused VM vessels support tumor growth. Only NOTCH-active non-NE cells are VM-competent and exhibit characteristics related to blood vessel development and extracellular matrix organization. On Matrigel, VM-primed non-NE cells remodel the extracellular matrix into hollow tubules through an integrin b1-dependent process.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Urology & Nephrology
Masaomi Nangaku, A. Richard Kitching, Peter Boor, Alessia Fornoni, Jurgen Floege, P. Toby Coates, Jonathan Himmelfarb, Rachel Lennon, Hans-Joachim Anders, Benjamin D. Humphreys, Fergus J. Caskey, Agnes B. Fogo
Summary: The International Society of Nephrology organized the TRANSFORM meeting to provide guidance on translational animal studies for new drug development in kidney disease. The meeting covered various themes such as disease model selection, pharmacokinetics, interventions, choice of animal, statistical power, organoids and organ-on-a-chip models, and reporting of results. These recommendations aim to accelerate the development of new drugs for efficacious diseases.
KIDNEY INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Alexander Eckersley, Mychel R. P. T. Morais, Matiss Ozols, Rachel Lennon
Summary: During ageing, there is a decline in the function of the glomerular and tubular basement membranes (BM) in the kidney, which is caused by damage accumulation to the extracellular matrix (ECM) protein structures. Peptide location fingerprinting (PLF) is used to identify ECM proteins with structure-associated differences in ageing. This study found alterations in functional regions of key BM components, reflecting age-dependent shifts in molecular and cellular interactions, oxidation, and the release of matrikines. The findings also revealed shared susceptibilities in BM components across species and organs.
Article
Cell Biology
Wen Y. Ding, Valeryia Kuzmuk, Sarah Hunter, Abigail Lay, Bryony Hayes, Matthew Beesley, Ruth Rollason, Jennifer A. Hurcombe, Fern Barrington, Catrin Masson, William Cathery, Carl May, Jack Tuffin, Timothy Roberts, Geraldine Mollet, Colin J. Chu, Jenny McIntosh, Richard J. Coward, Corinne Antignac, Amit Nathwani, Gavin I. Welsh, Moin A. Saleem
Summary: Gene therapy using AAV vector has successfully addressed the challenges of kidney diseases, showing particular success in targeting monogenic diseases in other organs. By utilizing AAV-LK03 and AAV 2/9, gene therapy has been able to rescue genetic defects and improve kidney disease in human and mouse models, establishing the podocyte as a viable target for gene therapy.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Marija Loncaric, Nikolina Stojanovic, Anja Rac-Justament, Kaatje Coopmans, Dragomira Majhen, Jonathan D. D. Humphries, Martin J. J. Humphries, Andreja Ambriovic-Ristov
Summary: This study found that KANK1 is not a component of the CMSC associated with integrin alpha V beta 5 FAs, and its knockout does not affect microtubule growth velocity or cell sensitivity to PTX. Knockout of talin2, similar to KANK2 knockout, disrupts actin-microtubule crosstalk, resulting in increased microtubule growth velocity, increased sensitivity to PTX, and reduced cell migration. Therefore, talin2 and KANK2 may be potential therapeutic targets for improved cancer therapy.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2023)
Article
Multidisciplinary Sciences
Irena Audzeyenka, Maria Szrejder, Dorota Rogacka, Stefan Angielski, Moin A. A. Saleem, Agnieszka Piwkowska
Summary: This study found that human podocytes express the BAIBA receptor MRGPRD, and stimulation with BAIBA can improve the respiratory parameters and promote mitochondrial dynamics in podocytes, indicating the importance of mitochondrial function in maintaining the renal filtration barrier.
SCIENTIFIC REPORTS
(2023)
Review
Physiology
Natalie C. Finch, Chris R. Neal, Gavin I. Welsh, Rebecca R. Foster, Simon C. Satchell
Summary: The fenestrations of glomerular endothelial cells (GEnCs) are crucial for the function of the glomerular filtration barrier. This review provides an update on the current understanding of the regulation and biogenesis of fenestrations and discusses the diseases in which loss of GEnC fenestrations may contribute to loss of glomerular filtration function. The literature reviewed includes studies on GEnCs as well as other cell types with similar fenestration structures, such as liver sinusoidal endothelial cells.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
