Article
Physiology
Molly A. Bingham, Kim Neijman, Chin -Rang Yang, Angel Aponte, Angela Mak, Hiroaki Kikuchi, Hyun Jun Jung, Brian G. Poll, Viswanathan Raghuram, Euijung Park, Chung -Lin Chou, Lihe Chen, Jens Leipziger, Mark A. Knepper, Margo Dona
Summary: The circadian variability in kidney function is often ignored in physiological experiments. This study used transcriptomics and proteomics to identify genes and proteins in the kidney that show circadian rhythms. These data have been made available as user-friendly web resources.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Review
Cell Biology
Min Chen, Xiangchen Gu
Summary: Endocytosis plays a crucial role in kidney diseases, particularly in renal fibrosis, and is affected by other diseases and factors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Urology & Nephrology
Lihe Chen, Chung-Lin Chou, Chin-Rang Yang, Mark A. Knepper
Summary: This study investigated sex differences in kidney physiology and pathophysiology using RNA-seq, ATAC-seq, and protein mass spectrometry methods. The results revealed significant differences in gene expression and chromatin accessibility in the proximal tubules between males and females. Many of the differentially expressed genes are involved in metabolic processes and transport functions. The study also identified several transcription factors and proteins that contribute to sex differences. The findings provide valuable insights into the regulatory mechanisms underlying sex differences in kidney function.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Multidisciplinary Sciences
Louisa M. S. Gerhardt, Jing Liu, Kari Koppitch, Pietro E. Cippa, Andrew P. McMahon
Summary: The study found that even mild to moderate ischemia-reperfusion injury can cause lasting damage, spreading from the cortico-medullary boundary (CMB) to cortical regions, and the remaining failed-repair PTCs may be triggers for chronic disease progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Shiting Liang, Youliang Wang, Meixia Kang, Juan Deng, Liting Chen, Xizhen Hong, Fan Fan Hou, Fujian Zhang
Summary: Protein reabsorption in renal proximal tubules is crucial for maintaining nutrient balance. We developed a new mouse model, AMN (CreERT2) knock-in mice, which express a fusion protein of Cre recombinase and estrogen receptor under the control of the AMN gene promoter specifically in renal proximal tubules. This model allows for the conditional knockout of genes in renal proximal tubules, providing valuable insights into their physiological function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Chemistry, Medicinal
Muyao Ye, Ming Yang, Wenni Dai, Hao Li, Xun Zhou, Yinyin Chen, Liyu He
Summary: Obesity-related glomerulopathy (ORG) is a secondary kidney damage caused by obesity, and there is currently a lack of effective strategies to prevent and delay its development. This article reviews the pathological characteristics of ORG, describes the roles of lipid metabolism disorders and mitochondrial oxidative stress in its development, and suggests potential therapeutic targets for ORG treatment.
Article
Biochemistry & Molecular Biology
Shreya T. Mukherji, Luca Brambilla, Kailey B. Stuart, Isabella Mayes, Laura C. Kutz, Yiliang Chen, Leandro A. Barbosa, Ibrahim Elmadbouh, Jeff P. McDermott, Steven T. Haller, Michael F. Romero, Manoocher Soleimani, Jiang Liu, Joseph I. Shapiro, Gustavo V. Blanco, Zijian Xie, Sandrine V. Pierre
Summary: Through ATP-dependent ion pumping, basolateral Na/K-ATPase (NKA) generates a Na+ gradient that drives apical Na+ reabsorption in the renal proximal tubule (RPT), while NKA signaling function triggers cellular redistribution and decreases Na+ reabsorption. Knockdown of RPT NKA leads to increased membrane NHE3 and NBCe1A, resulting in decreased urine output and Na+ excretion, elevated blood pressure, and increased RPT Na+ reabsorption. NKA signaling plays an important role in regulating Na+ reabsorption in RPT, functioning dominantly over NKA ion pumping.
Review
Cell Biology
Zahraa S. Hotait, Julia N. Lo Cascio, Elijah N. D. Choos, Blythe D. Shepard
Summary: The renal proximal tubule plays a crucial role in solute reabsorption and glucose metabolism. Understanding these processes helps unravel the mechanisms underlying renal diseases and explore potential therapeutic approaches.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Physiology
Hao Liu, Qi Sun, Zheng Ding, Wensen Shi, Wen-Hui Wang, Chengbiao Zhang
Summary: This study found that adenosine activates the basolateral K+ channels in the proximal tubules of mice through adenosine A1 receptor, and the mechanism of action is mediated by the PLC-PKC signaling pathway.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Medicine, General & Internal
Xiaohong Xiang, Jiefu Zhu, Gang Zhang, Zhengwei Ma, Man J. Livingston, Zheng Dong
Summary: The study demonstrates that p53 plays a critical role in kidney injury associated with cold storage/transplantation, and inhibiting p53 can improve the histology and function of transplanted kidneys, showing potential as a therapeutic target for kidney transplantation.
FRONTIERS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ramkumar Thiyagarajan, Mary Taub
Summary: Cystinosis is a genetic disease that causes renal failure. Study using human-induced pluripotent stem cells found that the differentiation ability of cystinotic cells is impaired, which may lead to the malfunctioning of renal proximal tubule.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Bolin Jing, Lei Yan, Jiajia Li, Piaopiao Luo, Xiaoni Ai, Pengfei Tu
Summary: A high-throughput human renal proximal tubule model based on an integrated biomimetic array chip (iBAC) demonstrated improved epithelial polarization and membrane transporter activity, offering a more accurate prediction of nephrotoxicity.
Article
Virology
Ping An, Maria Teresa Saenz Robles, Paul G. Cantalupo, Abhijit S. Naik, Rachel Sealfon, Michael J. Imperiale, James M. Pipas
Summary: BK virus infection is asymptomatic for most individuals but poses a threat to transplant patients and those with immunosuppressive disorders. Renal proximal tubule epithelial cells (RPTE) are permissive to BKV and have been widely used to study BKV infection. Results show that both primary and immortalized RPTE exhibit similar gene expression patterns and response to BKV infection, indicating that BKV preferentially replicates in injured or stressed kidney epithelial cells.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Celina Kruszniewska-Rajs, Barbara Strzalka-Mrozik, Magdalena Kimsa-Dudek, Agnieszka Synowiec-Wojtarowicz, Elwira Chrobak, Ewa Bebenek, Stanislaw Boryczka, Stanislaw Gluszek, Joanna Magdalena Gola
Summary: The study found that betulin and its derivatives affect the viability and antioxidant system of human renal proximal tubule epithelial cells, with betulin significantly reducing the cells' antioxidant capacity, while its derivatives have different impacts on the antioxidant system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Kristan H. Cleveland, Rick G. Schnellmann
Summary: Mitochondrial dysfunction is responsible for the development and progression of diabetic kidney disease (DKD). This study investigates the signaling mechanisms through which the beta 2-adrenergic receptor (AR) agonist formoterol restores mitochondrial fission/fusion proteins Drp1 and Mfn1. The results show that formoterol acts through separate but integrated pathways to promote mitochondrial biogenesis, decrease fission, and increase fusion in renal proximal tubule cells (RPTC) treated with high glucose, suggesting its potential as a therapeutic for DKD.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Toxicology
Wanda van der Stel, Huan Yang, Nanette G. Vrijenhoek, Johannes P. Schimming, Giulia Callegaro, Giada Carta, Salihanur Darici, Johannes Delp, Anna Forsby, Andrew White, Sylvia le Devedec, Marcel Leist, Paul Jennings, Joost B. Beltman, Bob van de Water, Erik H. J. Danen
Summary: Research shows that CI and CIII inhibitors affect mitochondrial functionality and cellular ATP levels, resulting in decreased cell viability, while CII inhibitors do not have this effect.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Toxicology
Sylvia E. Escher, Alejandro Aguayo-Orozco, Emilio Benfenati, Annette Bitsch, Thomas Braunbeck, Katharina Brotzmann, Frederic Bois, Bart van der Burg, Jose Castel, Thomas Exner, Domenico Gadaleta, Iain Gardner, Daria Goldmann, Oliver Hatley, Nazanin Golbamaki, Rabea Graepel, Paul Jennings, Alice Limonciel, Anthony Long, Richard Maclennan, Enrico Mombelli, Ulf Norinder, Sankalp Jain, Liliana Santos Capinha, Olivier T. Taboureau, Laia Tolosa, Nanette G. Vrijenhoek, Barbara M. A. Van Vugt-Lussenburg, Paul Walker, Bob van de Water, Matthias Wehr, Andrew White, Barbara Zdrazil, Ciaran Fisher
Summary: Read-across approaches may not provide sufficient evidence on a common mode of action across category members. A case study on branched aliphatic carboxylic acids shows the potential to induce hepatic steatosis. By analyzing gene expression patterns and adverse outcome pathways, researchers were able to confirm biological similarity and design an in vitro testing battery to systematically investigate a common mode of action among the compounds.
TOXICOLOGY IN VITRO
(2022)
Article
Toxicology
Cleo Tebby, Wang Gao, Johannes Delp, Giada Carta, Wanda van der Stel, Marcel Leist, Paul Jennings, Bob van de Water, Frederic Y. Bois
Summary: This study used quantitative Adverse Outcome Pathways (qAOPs) and mathematical models to calibrate the mitochondrial toxicity of two chemicals in different cell lines. The results showed that there were practical difficulties in calibrating qAOPs in different cell types, and even when the same key event readouts were measured, the mathematical functions used may not be the same. Cross-validation also revealed underestimation of toxicity in LHUMES cells.
TOXICOLOGY IN VITRO
(2022)
Article
Toxicology
Carolina Nunes, Pranika Singh, Zahra Mazidi, Cormac Murphy, Aurore Bourguignon, Sara Wellens, Vidya Chandrasekaran, Sreya Ghosh, Melinda Zana, David Pamies, Aurelien Thomas, Catherine Verfaillie, Maxime Culot, Andras Dinnyes, Barry Hardy, Anja Wilmes, Paul Jennings, Regina Grillari, Johannes Grillari, Marie-Gabrielle Zurich, Thomas Exner
Summary: This article proposes an in vitro multi-organ strategy to assess the toxicity of chemicals using human induced pluripotent stem cells (hiPSCs)-derived models. The strategy allows parallel evaluation of chemical toxicity on multiple tissues/organs, exclusively in human cells, eliminating interspecies bias and increasing the chance to identify toxic compounds. The authors demonstrated the strategy by generating models of brain, blood-brain barrier, kidney, liver, and vasculature and exposing them to paraquat, highlighting their differential cytotoxic sensitivity and the deregulation of key signaling pathways.
TOXICOLOGY IN VITRO
(2022)
Review
Chemistry, Medicinal
Barbara M. A. van Vugt-Lussenburg, Liliana Capinha, Jelle Reinen, Martijn Rooseboom, Michel Kranendonk, Rob C. A. Onderwater, Paul Jennings
Summary: Understanding the metabolism, distribution, and elimination of exogenous chemicals is crucial in determining their impact on the human body. Jan Commandeur and his colleagues' research has significantly contributed to the understanding of the metabolism of important compounds and the development of techniques for studying xenobiotic metabolism.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Editorial Material
Toxicology
Walter Pfaller, Paul Jennings
Summary: Science should consider the long-term consequences to human society and the environment, rather than solely focusing on feasibility. Scientists should take responsibility for the consequences of their discoveries and conduct ethical evaluations.
TOXICOLOGY IN VITRO
(2022)
Article
Biochemistry & Molecular Biology
Ismael Obaidi, Alfonso Blanco Fernandez, Tara McMorrow
Summary: This study utilized curcumin to enhance the sensitivity of TRAIL-resistant kidney cancer cells and investigated the molecular mechanisms involved. Curcumin targeted the ACHN cell cycle and cellular metabolism by regulating the expression of let-7C.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Reproductive Biology
Francesca Pistollato, Anna Bal-Price, Sandra Coecke, Surat Parvatam, David Pamies, Katherine Czysz, Jie Hao, Kehkooi Kee, Adrian Kee Keong Teo, Shuaishuai Niu, Anja Wilmes, Lena Smirnova, Christian Freund, Christine Mummery, Glyn Stacey
Summary: The advent of human pluripotent stem cell technology has provided the potential to develop human models for better understanding of human development and disease mechanisms. These models can be used to study the biological processes of the human body and improve strategies for diagnosis, prevention, therapies, and precision medicine. Quality control measures and appropriate markers are crucial for ensuring reproducibility of scientific data derived from pluripotent stem cell-based systems.
REPRODUCTIVE TOXICOLOGY
(2022)
Article
Toxicology
Liliana Capinha, Yaran Zhang, Anna-Katharina Holzer, Anna-Katharina Uckert, Melinda Zana, Giada Carta, Cormac Murphy, Jenna Baldovini, Zahra Mazidi, Johannes Grillari, Andras Dinnyes, Bob van de Water, Marcel Leist, Jan N. M. Commandeur, Paul Jennings
Summary: This study used six human derived cell models to investigate the effects of trichloroethylene (TCE) S-conjugates. The results showed that TCE S-conjugates induced Nrf2 pathway and unfolded protein response, which may explain the nephrotoxicity and neurotoxicity of TCE. This study expands our knowledge on the tissue specificity of TCE S-conjugates and highlights the value of human cell models and transcriptomics in mechanistic studies.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Cell Biology
Paul Jennings, Giada Carta, Pranika Singh, Daniel da Costa Pereira, Anita Feher, Andras Dinnyes, Thomas E. E. Exner, Anja Wilmes
Summary: Through transcriptomic analysis, this study investigated the time-dependent changes in gene expression levels in iPSC-derived renal cells treated with different compounds, and identified the early response of key genes involved in cellular stress response pathways. The findings highlight the application of iPSC cells for predicting cellular toxicity and provide new insights into the temporal and early effects of key genes in cellular stress response pathways.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Veronica Ibanez Gaspar, Tara McMorrow
Summary: Cancer cells have high levels of oxidative stress, and an increase in reactive oxygen species (ROS) can lead to both apoptosis and cell invasion. This can be attributed to the impact on MMP-2/MMP-9 activity caused by the increase in ROS H2O2, which degrades the extracellular matrix. Curcumin, although limited in bioavailability, has shown anticancer effects and can sensitize kidney cancer cells to TRAIL-induced apoptosis. This study demonstrates that the curcuminoid EF24, in combination with TRAIL, reduces intracellular H2O2 and MMP-2/MMP-9 activity in the renal adenocarcinoma cell line ACHN by increasing peroxidase activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Toxicology
Liliana Capinha, Paul Jennings, Jan N. M. Commandeur
Summary: Bioactivation of trichloroethylene (TCE) through glutathione conjugation can cause adverse effects in the kidney and other extrahepatic tissues. Among the three regioisomeric conjugates formed, only 1,2-trans-DCVG and its corresponding cysteine-conjugate have been extensively studied. This study investigates the metabolism and cellular effects of 1,2-cis-DCVG and 1,2-cis-DCVC for the first time, revealing lower toxicity and slower formation rate for 1,2-cis-DCVC compared to 1,2-trans-DCVC.
TOXICOLOGY LETTERS
(2023)
Article
Medicine, Research & Experimental
Cormac Murphy, Elisabeth Naderlinger, Amber Mater, Roelof J. C. Kluin, Anja Wilmes
Summary: Human induced pluripotent stem cells (hiPSCs) show potential for replacing animal models in toxicology, but their culture and differentiation depend on extracellular matrix (ECM) coating. Matrigel, the most widely used ECM, has drawbacks such as batch variations and ethical concerns. This study compares three commercially available human ECM coatings (vitronectin, laminin-511, and laminin-521) to Matrigel for hiPSC maintenance and differentiation into renal podocyte-like cells. Results show that all tested coatings are comparable to Matrigel, and decellularized fibroblast-ECM is a promising low-cost alternative.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2023)