Article
Urology & Nephrology
Janina Mueller-Deile, Nina Sopel, Alexandra Ohs, Victoria Rose, Marwin Groener, Christoph Wrede, Jan Hegermann, Christoph Daniel, Kerstin Amann, Gunther Zahner, Mario Schiffer
Summary: This study demonstrates that miR-192-5p and miR-378a-3p are upregulated in the glomeruli of iMGN patients, while NPNT is reduced. Using zebrafish and mouse models, it was shown that overexpression of miR-192-5p and knockdown of npnt induced edema, proteinuria, and podocyte damage. GEC downregulates podocyte NPNT via exosomes containing miR-192-5p.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Qiong-Dan Hu, Hong-Lian Wang, Jian Liu, Tao He, Rui-Zhi Tan, Qiong Zhang, Hong-Wei Su, Fahsai Kantawong, Hui-Yao Lan, Li Wang
Summary: Btg2 plays a pathogenic role in FSGS by promoting podocyte injury through a Smad3-dependent epithelial-mesenchymal transition pathway.
Article
Urology & Nephrology
Fang Li, Yili Fang, Qiyuan Zhuang, Meichu Cheng, Desmond Moronge, Hao Jue, Oded Meyuhas, Xiaoqiang Ding, Zhigang Zhang, Jian-Kang Chen, Huijuan Wu
Summary: The phosphorylation of ribosomal protein S6 (rpS6) plays a crucial role in podocyte hypertrophy and loss during the pathogenesis of focal segmental glomerulosclerosis (FSGS). Inhibiting rpS6 phosphorylation can effectively attenuate podocyte hypertrophy and depletion, thereby reducing the formation of FSGS lesions.
KIDNEY INTERNATIONAL
(2022)
Article
Genetics & Heredity
David Marx, Sophie Caillard, Jerome Olagne, Bruno Moulin, Thierry Hannedouche, Guy Touchard, Arnaud Dupuis, Christian Gachet, Anne Molitor, Seiamak Bahram, Raphael Carapito
Summary: A new nonsense variant in the PODXL gene associated with kidney disease was identified, characterized by FSGS features and glomerular basement membrane duplication. This study provides important insights into the pathophysiology of the disease through light and electron microscopy.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Immunology
Ibrahim Batal, Pascale Khairallah, Astrid Weins, Nicole K. Andeen, Michael B. Stokes
Summary: Primary focal segmental glomerulosclerosis (FSGS) is a disease characterized by diffuse podocyte foot process effacement and nephrotic syndrome. It can recur after transplantation and is associated with immunogenetic factors. This study retrospectively investigated a cohort of kidney allograft recipients with primary FSGS and found a higher frequency of HLA-A30 antigen in patients with primary FSGS compared to healthy controls and deceased kidney donors. The study also revealed an association between donor HLA-A30 and recurrent FSGS in transplant patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Urology & Nephrology
Ying Zhu, Yun Fan, Feng Xu, Shaoshan Liang, Dandan Liang, Ping Li, Yuanyuan Xia, Xiaodong Zhu, Fan Yang, Jinsong Chen, Caihong Zeng
Summary: In this study, 60.6% of TG patients were found to have concomitant FSGS, which was associated with more severe clinicopathological features and worse allograft survival. The presence of FSGS in TG patients was independently associated with higher proteinuria, serum creatinine levels, chronic glomerulopathy score, and a higher kidney allograft loss rate.
AMERICAN JOURNAL OF NEPHROLOGY
(2021)
Article
Urology & Nephrology
Mahmoud Kallash, Yujie Wang, Abigail Smith, Howard Trachtman, Rasheed Gbadegesin, Carla Nester, Pietro Canetta, Chen Wang, Tracy E. Hunley, C. John Sperati, David Selewski, Isabelle Ayoub, Tarak Srivastava, Amy K. Mottl, Jeffrey Kopp, Brenda Gillespie, Bruce Robinson, Dhruti Chen, Julia Steinke, Katherine Twombley, Kimberly Reidy, Krzysztof Mucha, Larry A. Greenbaum, Brooke Blazius, Margaret Helmuth, Peleg Yonatan, Rulan S. Parekh, Susan Hogan, Virginie Royal, Vivette D'Agati, Aftab Chishti, Ronald Falk, Ali Gharavi, Lawrence Holzman, Jon Klein, William Smoyer, Matthias Kretzler, Debbie Gipson, Jason M. Kidd
Summary: Background: FSGS is a heterogeneous diagnosis with a guarded prognosis. APOL1 gene polymorphisms are associated with developing FSGS and faster progression to kidney failure. Understanding the natural history of FSGS patients with APOL1 risk alleles is important for patient care and intervention studies.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Multidisciplinary Sciences
Takaya Ozeki, Michio Nagata, Takayuki Katsuno, Koji Inagaki, Kazunori Goto, Sawako Kato, Yoshinari Yasuda, Naotake Tsuboi, Shoichi Maruyama
Summary: This study analyzed the clinical implication of unclassified segmental lesions in Japanese adult patients with nephrotic syndrome compared to Columbia-classified FSGS. The results showed that unclassified segmental lesions may have equivalent clinical impact as Columbia classification of FSGS, with similar treatment responses and no significant difference in the decline of eGFR.
Article
Urology & Nephrology
Maximilian Schindler, Florian Siegerist, Tim Lange, Stefan Simm, Sophia-Marie Bach, Marianne Klawitter, Jochen Gehrig, Sheraz Gul, Nicole Endlich
Summary: This study developed a novel in vivo high-content screening assay using an FSGS-like zebrafish model, and identified belinostat and related pan-histone deacetylase inhibitors as potential drugs for treating FSGS.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Medicine, Research & Experimental
Su-Wei Hu, Yuan-Hung Wang, Jhy-Shrian Huang, Yea-Mey Yang, Chia-Chang Wu, Chao-Wen Cheng
Summary: The study found that vardenafil treatment can alleviate proteinuria, renal dysfunction, and hypercholesterolemia induced by focal segmental glomerulosclerosis, and improve the histopathological damage of the kidneys.
Review
Immunology
Anne K. Muehlig, Sydney Gies, Tobias B. Huber, Fabian Braun
Summary: This review summarizes the current knowledge on viral infections associated with collapsing glomerulopathy, with a special focus on the influence of systemic immune responses and potential mechanisms propagating its development.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Fabian Braun, Inka Homeyer, Nada Alachkar, Tobias B. Huber
Summary: Researchers summarized the current knowledge of immune effector cells, secreted soluble factors, and podocyte response in immune-mediated (primary) FSGS.
CELL AND TISSUE RESEARCH
(2021)
Article
Cell Biology
Lixia Wang, Jie Wang, Zhimin Wang, Jianhua Zhou, Yu Zhang
Summary: The study found that urine exosomal miR-193a levels were significantly higher in patients with primary FSGS compared to those with MCN and IgAN, and were positively correlated with glomerulosclerosis index. Exosomes from cultured podocytes could transport miR-193a-5p to recipient cells potentially through a calcium-dependent release mechanism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Urology & Nephrology
Jing Yang, Yongli Xu, Linxia Deng, Luowen Zhou, Liru Qiu, Yu Zhang, Jianhua Zhou
Summary: This study identified three cases of isolated proteinuria and FSGS caused by CUBN gene mutations, expanding the spectrum of renal manifestation and genotype of CUBN gene mutations.
Article
Urology & Nephrology
Manuel Rogg, Jasmin I. Maier, Clara Van Wymersch, Martin Helmstaedter, Alena Sammarco, Maja Lindenmeyer, Paulina Zareba, Eloi Montanez, Gerd Walz, Martin Werner, Nicole Endlich, Thomas Benzing, Tobias B. Huber, Christoph Schell
Summary: This study investigated the composition and regulation of podocyte integrin adhesion complexes and identified the important roles of PARVA and PARVB in maintaining the integrity of the filtration barrier. By using gene knockout experiments, the researchers revealed the impact of these proteins on podocytes and uncovered the adaptive mechanisms of podocyte integrin adhesion complexes.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Review
Urology & Nephrology
Richard W. Naylor, Mychel R. P. T. Morais, Rachel Lennon
Summary: The glomerular basement membrane (GBM) is crucial for kidney filtration, with studies revealing insights into its composition, assembly, developmental transitions, and filtration role. Defects in GBM components are associated with hereditary and acquired diseases, with current treatments focused on reducing intraglomerular pressure and addressing underlying causes. Therapies targeting GBM maintenance and repair could lead to new treatments for GBM-associated diseases.
NATURE REVIEWS NEPHROLOGY
(2021)
Article
Pediatrics
Charles Pickles, Amrit Kaur, Dean Wallace, Christian Brix, Rachel Lennon, Nicholas Plant, Mohan Shenoy
PEDIATRIC NEPHROLOGY
(2020)
Editorial Material
Urology & Nephrology
Rachel Lennon, Alessia Fornoni
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Endocrinology & Metabolism
Alexandra Pokhilko, Gaia Brezzo, Lahiru Handunnetthi, Raphael Heilig, Rachel Lennon, Colin Smith, Stuart M. Allan, Alessandra Granata, Sanjay Sinha, Tao Wang, Hugh S. Markus, Alexandra Naba, Roman Fischer, Tom Van Agtmael, Karen Horsburgh, M. Zameel Cader
Summary: This study successfully extracted cerebrovascular ECM from mouse and human brain tissues and identified over 1000 proteins in the ECM-enriched fraction. The identification of 147 core ECM proteins in the human brain vascular matrisome and the connection between brain ECM proteins and cerebrovascular diseases, provides unique mechanistic insight and potential drug targets for cerebrovascular diseases.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Urology & Nephrology
Michael J. Randles, Franziska Lausecker, Qingyang Kong, Hani Suleiman, Graeme Reid, Maria Kolatsi-Joannou, Bernard Davenport, Pinyuan Tian, Sara Falcone, Paul Potter, Tom Van Agtmael, Jill T. Norman, David A. Long, Martin J. Humphries, Jeffrey H. Miner, Rachel Lennon
Summary: Ultrastructural changes in basement membranes are associated with altered cell adhesion and metabolic processes, and distinct matrix proteomes were identified in aging and kidney disease progression in mice. Basement membrane components were reduced while interstitial matrix proteins were increased, a pattern also observed in human kidney aging and disease datasets. This study provides insight into mechanisms of response to kidney injury and repair.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Urology & Nephrology
Yuka Takemon, Valerie Wright, Bernard Davenport, Daniel M. Gatti, Susan M. Sheehan, Kelsey Letson, Holly S. Savage, Rachel Lennon, Ron Korstanje
Summary: This study identified modifier genes for X-linked Alport Syndrome using a novel genetic approach in mice. The candidate modifier gene Fmn1 was validated, showing its potential role in reducing albuminuria and podocyte protrusions. This approach can be applied to identify modifier genes for other forms of kidney disease, providing new therapeutic targets.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Immunology
Tara E. Sutherland, Tovah N. Shaw, Rachel Lennon, Sarah E. Herrick, Dominik Rueckerl
Summary: Peritoneal dialysis initially benefits patients with chronic kidney disease, but long-term use may lead to significant pathology, increasing the risk of infection and inflammation.
FRONTIERS IN IMMUNOLOGY
(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
Rebecca Preston, Qing-Jun Meng, Rachel Lennon
Summary: The circadian clock network in mammals is responsible for regulating various physiological processes in the body. Kidney disease is associated with the circadian system and extracellular matrix. Recent evidence suggests that cell-matrix interactions and the biomechanical properties of the matrix play a crucial role in regulating peripheral circadian rhythms. Studying the kidney matrisome can provide insights into the interactions between the extracellular matrix and intracellular time-keeping mechanisms.
Article
Pediatrics
Richard W. Naylor, Elizabeth Watson, Samantha Williamson, Rebecca Preston, J. Bernard Davenport, Nicole Thornton, Martin Lowe, Maggie Williams, Rachel Lennon
Summary: A novel homozygous truncating variant in CD151 was identified in a young child with nail dystrophy and persistent urinary tract infections presenting with nephrotic-range proteinuria. The imaging of patient kidney tissue revealed thickening of GBM and podocyte effacement. Functional testing in zebrafish confirmed that depletion of cd151 caused proteinuria, indicating the association of CD151 variant with nephrotic-range proteinuria and microscopic hematuria.
PEDIATRIC NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Ranjay Jayadev, Mychel R. P. T. Morais, Jamie M. Ellingford, Sandhya Srinivasan, Richard W. Naylor, Craig Lawless, Anna S. Li, Jack F. Ingham, Eric Hastie, Qiuyi Chi, Maryline Fresquet, Nikki-Maria Koudis, Huw B. Thomas, Raymond T. O'Keefe, Emily Williams, Antony Adamson, Helen M. Stuart, Siddharth Banka, Damian Smedley, David R. Sherwood, Rachel Lennon
Summary: By utilizing bioinformatic and in vivo approaches, we have identified a network of proteins involved in basement membrane regulation and function. This study highlights the complexity of basement membranes and their impact on human health.
Article
Urology & Nephrology
Richard W. Naylor, Emmanuel Lemarie, Anthony Jackson-Crawford, J. Bernard Davenport, Aleksandr Mironov, Martin Lowe, Rachel Lennon
Summary: Zebrafish is a valuable model for studying kidney dysfunction. Researchers in this study created a transgenic zebrafish line that can quantitatively measure proteinuria, providing a new tool for screening drugs to alleviate proteinuria.
KIDNEY INTERNATIONAL
(2022)
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
Multidisciplinary Sciences
Maryline Fresquet, Michael P. Lockhart-Cairns, Samuel J. Rhoden, Thomas A. Jowitt, David C. Briggs, Clair Baldock, Paul E. Brenchley, Rachel Lennon
Summary: Membranous nephropathy is an autoimmune kidney disease caused by autoantibodies targeting antigens present on glomerular podocytes. This study provides insights into the structure and key residues of the phospholipase A2 receptor (PLA2R) involved in autoantibody binding, and suggests potential drug targets for membranous nephropathy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)