Article
Biochemistry & Molecular Biology
Takwa S. Aroankins, Sathish K. Murali, Robert A. Fenton, Qi Wu
Summary: This study revealed protein post-translational modifications by SUMOylation in the aldosterone-sensitive kidney distal convoluted tubule, highlighting the important role of SUMOylation in the physiological regulation of Pept2 trafficking by aldosterone.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Urology & Nephrology
Eszter Banki, Viktoria Fisi, Sandra Moser, Agnieszka Wengi, Monique Carrel, Dominique Loffing-Cueni, David Penton, Denise V. Kratschmar, Ludovica Rizzo, Soeren Lienkamp, Alex Odermatt, Markus M. Rinschen, Johannes Loffing
Summary: The study revealed the critical role of calcineurin in the function of the distal convoluted tubule (DCT), with the deletion of the relevant genes impacting the expression of specific proteins and signaling pathways in the DCT. The findings provide new insights into the pathophysiology of calcineurin inhibitor side effects and the molecular players involved in the DCT.
KIDNEY INTERNATIONAL
(2021)
Article
Cell Biology
Viktor N. Tomilin, Kyrylo Pyrshev, Naghmeh Hassanzadeh Khayyat, Oleg Zaika, Oleh Pochynyuk
Summary: The kidneys play a central role in regulating potassium homeostasis, with WNK kinases, especially WNK1, being involved in K+ balance. TRPV4 channel has been found to be essential for BK activation in the aldosterone-sensitive distal nephron. Inhibition of WNK kinase decreased TRPV4-dependent Ca2+ influx, and WNK1 was shown to regulate TRPV4 activity and its stimulation by aldosterone.
Article
Physiology
Serena Milano, Monica Carmosino, Andrea Gerbino, Ilenia Saponara, Dominga Lapi, Massimo Dal Monte, Paola Bagnoli, Maria Svelto, Giuseppe Procino
Summary: The study revealed that BAR3 plays a novel role in regulating NCC in DCT, with its knockout leading to reduced NCC phosphorylation and decreased SPAK and WNKs activation. Conversely, BAR1/2 knockout resulted in reduced NCC abundance with no change in phosphorylation. Additionally, selective BAR3 agonism promoted SPAK and NCC activation in wild-type mouse kidney slices.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Urology & Nephrology
Lihe Chen, Chun-Lin Chou, Mark A. Knepper
Summary: Single-cell transcriptomics analysis revealed unexpected diversity among the cells of the distal nephron in mice, identifying differences between DCT1 and DCT2 cells, as well as subtypes of CTAL cells.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Physiology
Ryan J. Cornelius, Jonathan W. Nelson, Xiao-Tong Su, Chao-Ling Yang, David H. Ellison
Summary: Cullin-RING ligases are a type of E3 ubiquitin ligases that control cellular processes by regulating degradation. Genetic deletion of renal-specific genes results in a reduction of NCC due to hypoplasia of the DCT, which coincides with cortical kidney injury.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Article
Urology & Nephrology
Joonho Yoon, Zhenan Liu, Eunyoung Lee, Liping Liu, Silvia Ferre, Johanne Pastor, Jianning Zhang, Orson W. Moe, Audrey N. Chang, R. Tyler Miller
Summary: The study revealed a novel physiologic mechanism for the regulation of soluble Klotho levels by the renal CaSR-ADAM10-Klotho pathway. It was found that CaSR activators, including alkaline substances, increase renal CaSR-stimulated Klotho shedding. This mechanism is predicted to be relevant to the effects of acidosis and alkali therapy on chronic kidney disease progression.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Physiology
Ava M. Zapf, Paul R. Grimm, Lama Al-Qusairi, Eric Delpire, Paul A. Welling
Summary: Aberrant activation of the WNK-SPAK signaling pathway in the DCT causes familial hyperkalemic hypertension. The synthesis of PGE2 is increased in this process and inhibits the expression of RomK through the EP1 receptor. These findings reveal the mechanism by which sodium transport activation in the DCT leads to remodeling of the ASDN.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Urology & Nephrology
Jen-Chi Chen, Meng-Xuan Lin, Chih-Jen Cheng
Summary: Recent efforts have identified WNK4 as a physiological intracellular chloride sensor and regulators of intracellular chloride concentration in the distal convoluted tubule. WNK4 emerges as the leading candidate of the chloride sensor in DCT due to its highest chloride sensitivity and dominant expression. The chloride-mediated WNK4 regulations explain the inverse relationship between dietary potassium intake and NCC activity.
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
(2021)
Article
Engineering, Biomedical
A. M. van Genderen, M. G. Valverde, P. E. Capendale, M. Kersten, E. Sendino Garvi, C. C. L. Schuurmans, M. Ruelas, J. T. Soeiro, G. Tang, M. J. Janssen, J. Jansen, S. M. Mihaila, T. Vermonden, Y. S. Zhang, R. Masereeuw
Summary: This study proposes a coaxial printing method to obtain microfibers resembling the architecture of the proximal tubule (PT). These printed microfibers show stable structure and cytocompatibility in culture, and can be used to mimic two genotypes of PT in the study of kidney disorders. The engineered PT exhibits homogenous cytoskeleton organization, barrier-formation, and polarization, as well as reduced apical transport activity in the disease model. The system holds great promise for further research in establishing advanced in vitro disease models.
Review
Cell & Tissue Engineering
Charlotte J. A. Olde Hanhof, Fjodor A. Yousef Yengej, Maarten B. Rookmaaker, Marianne C. Verhaar, Jenny van der Wijst, Joost G. Hoenderop
Summary: The kidneys play a crucial role in maintaining electrolyte homeostasis, with the distal convoluted tubule (DCT) and connecting tubule being important for regulating sodium, magnesium, and calcium excretion. Advances in research techniques have led to the development of kidney organoids and tubuloids as new models for studying DCT physiology, offering promising opportunities for disease modeling and personalized medicine. There is a need for advanced human cell models to further understand the complex physiology of the DCT segment.
TISSUE ENGINEERING PART C-METHODS
(2021)
Article
Biochemistry & Molecular Biology
Stale Ellingsen, Shailesh Narawane, Anders Fjose, Tiziano Verri, Ivar Ronnestad
Summary: The study investigated the absorption of amino acids in mammals and zebrafish by the system b(0,+), as well as the mutations in these genes causing diseases. The expression patterns of slc3a1 and slc7a9 genes in zebrafish during early development and their role in organ growth were highlighted.
FISH PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Physiology
Marta Ortega-Martinez, Vanessa Gutierrez-Davila, Esthefania Gutierrez-Arenas, Alberto Niderhauser-Garcia, Ricardo M. Cerda-Flores, Gilberto Jaramillo-Rangel
Summary: This study analyzed whether there are significant differences in the diameter and area of the proximal convoluted tubule (PCT) and distal convoluted tubule (DCT) depending on whether they are considered circular or elliptical in shape. The results showed significant differences in diameter and area between circular and elliptical shapes, suggesting that the convoluted tubules of the nephron should be considered elliptical rather than circular in stereological studies of the kidney. Care should be taken when evaluating the diameters and areas of these tubules.
KIDNEY & BLOOD PRESSURE RESEARCH
(2021)
Article
Physiology
Yu Xiao, Xin-Peng Duan, Dan-Dan Zhang, Wen-Hui Wang, Dao-Hong Lin
Summary: Basolateral Kir4.1/Kir5.1 in the distal convoluted tubule plays a crucial role in detecting high potassium levels and regulating renal potassium excretion. The Nedd4-2 gene mediates the effect of potassium intake on Kir4.1/Kir5.1 and NaCl cotransporter, as demonstrated by the lack of inhibition of these channels in kidney tubule-specific Nedd4-2 knockout mice under high potassium intake.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Biology
E. A. Gallafassi, M. B. Bezerra, N. A. Reboucas
Summary: DCT contains NCC, which is inhibited by thiazide diuretics. WNK1 and WNK4 activate NCC and cause hypokalemia and hypertension. WNK4 phosphorylates NCC through the activation of SPAK/OSR1 kinases, and its activity is regulated by changes in intracellular Cl- concentration.
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2023)
Article
Transplantation
Rosa Vargas-Poussou, Felix Claverie-Martin, Caroline Prot-Bertoye, Valentina Carotti, Jenny van der Wijst, Ana Perdomo-Ramirez, Gloria M. Fraga-Rodriguez, Marguerite Hureaux, Caro Bos, Femke Latta, Pascal Houillier, Joost G. J. Hoenderop, Jeroen H. F. de Baaij
Summary: This study identifies TRPM7 as a potential candidate gene for hereditary HSH, and the mutations in TRPM7 gene result in impaired magnesium transport, leading to hypomagnesaemia and secondary hypocalcaemia.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Multidisciplinary Sciences
Barnabas P. Ilenwabor, Heidi Schigt, Andreas Kompatscher, Caro Bos, Malou Zuidscherwoude, Bram C. J. van der Eerden, Joost G. J. Hoenderop, Jeroen H. F. de Baaij
Summary: Autosomal dominant mutations in FAM111A cause Kenny-Caffey syndrome type 2, characterized by growth retardation and electrolyte imbalance. This study found that mice lacking the FAM111A gene maintained normal electrolyte balance on a standard diet.
SCIENTIFIC REPORTS
(2022)
Article
Urology & Nephrology
Uyenlinh L. Mirshahi, Ahana Bhan, Lotte E. Tholen, Brian Fang, Guoli Chen, Bryn Moore, Adam Cook, Prince Mohan Anand, Kashyap Patel, Mary E. Haas, Luca A. Lotta, Peter Igarashi, Jeroen H. F. de Baaij, Silvia Ferre, Joost G. J. Hoenderop, David J. Carey, Alexander R. Chang
Summary: This study provides evidence for the pathogenicity of HNF1B-p.Arg303His by thoroughly evaluating the variant and ruling out other variants. The results demonstrate similar burden of kidney manifestations to known HNF1B pathogenic variants and a greater burden compared to noncarriers.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Urology & Nephrology
Daan H. H. M. Viering, Marguerite Hureaux, Kornelia Neveling, Femke Latta, Michael Kwint, Anne Blanchard, Martin Konrad, Rene J. M. Bindels, Karl-Peter Schlingmann, Rosa Vargas-Poussou, Jeroen H. F. de Baaij
Summary: This study identified intronic pathogenic variants in Gitelman syndrome through long-read sequencing, which can provide a higher accuracy and feasibility for the diagnosis of this disease.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lotte E. E. Tholen, Heidi Schigt, Sanne G. E. Kleuskens, Caro Bos, Cornelia G. G. Spruijt, Brigith Willemsen, Michiel Vermeulen, Joost G. J. Hoenderop, Jeroen H. F. de Baaij
Summary: We identified BAIAP2L2 as a novel transcriptional target of HNF1 beta, which plays a role in maintaining epithelial cell integrity in the kidney.
Review
Physiology
Anastasia Adella, Jeroen H. F. de Baaij
Summary: The mammalian target of rapamycin (mTOR) signaling pathway is crucial for maintaining cell growth and metabolism, especially in the kidney. Different segments of the renal tubule have different roles for mTORC1 and mTORC2 in regulating nutrient transport, NKCC2 expression and activity, and Na+ reabsorption and K+ excretion. However, the upstream activators of mTOR signaling in most nephron segments remain elusive, and further understanding of growth factor signaling and nutrient sensing is essential to establish the exact role of mTOR in kidney physiology.
Item Withdrawal
Endocrinology & Metabolism
Heidi Schigt, Martin Bald, Bram C. J. van der Eerden, Lars Gal, Barnabas P. Ilenwabor, Martin Konrad, Michael A. Levine, Dong Li, Christoph J. Mache, Sharon Mackin, Colin Perry, Francisco J. Rios, Karl Peter Schlingmann, Ben Storey, Christine M. Trapp, Annemieke J. M. H. Verkerk, M. Carola Zillikens, Rhian M. Touyz, Ewout J. Hoorn, Joost G. J. Hoenderop, Jeroen H. F. de Baaij
Summary: This article has been withdrawn and duplicated due to a publisher error. The definitive version of the article can be found at https://doi.org/10.1210/clinem/dgad147.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Heidi Schigt, Martin Bald, Bram C. J. van der Eerden, Lars Gal, Barnabas P. Ilenwabor, Martin Konrad, Michael A. Levine, Dong Li, Christoph J. Mache, Sharon Mackin, Colin Perry, Francisco J. Rios, Karl Peter Schlingmann, Ben Storey, Christine M. Trapp, Annemieke J. M. H. Verkerk, M. Carola Zillikens, Rhian M. Touyz, Ewout J. Hoorn, Joost G. J. Hoenderop, Jeroen H. F. de Baaij
Summary: This study aimed to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders. Through clinical and genetic analysis of 10 KCS2 patients and a systematic review of 205 genetically confirmed KCS cases, it was found that there is substantial overlap in the phenotypic spectra of KCS1 and KCS2, but intellectual disability and abnormal bone phenotype are the most distinguishing features.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Linda C. A. Drenthen, Jeroen H. F. de Baaij, Laura Rodwell, Antonius E. van Herwaarden, Cees J. Tack, Bastiaan E. de Galan
Summary: This study aimed to investigate the effect of magnesium supplementation on insulin sensitivity in patients with type 2 diabetes. The results showed that despite a modest increase in serum magnesium concentration, oral magnesium supplementation did not improve insulin sensitivity in insulin-treated type 2 diabetes patients with low magnesium levels.
Review
Urology & Nephrology
Daan H. H. M. Viering, Lars Vermeltfoort, Rene J. M. Bindels, Jaap Deinum, Jeroen H. F. de Baaij
Summary: This systematic review investigated the presence of electrolyte disorders in patients with mitochondrial cytopathies and found that electrolyte disorders are commonly reported in these patients. The study highlights the importance of recognizing mitochondrial diseases as a cause of disturbances in electrolyte homeostasis.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Review
Physiology
Jeroen H. F. de Baaij
Summary: Mg2+ is crucial for various cellular and physiological processes. Recent studies on transgenic animal models and genetic disorders have provided insights into the molecular mechanisms of Mg2+ reabsorption in the kidney.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Physiology
Lotte E. Tholen, Femke Latta, Joost H. A. Martens, Joost G. J. Hoenderop, Jeroen H. F. de Baaij
Summary: Mutations in the HNF18 gene cause a rare and heterogeneous disease characterized by renal cysts, diabetes, and electrolyte disturbances. This study identified new targets of HNF18 that are involved in cell polarity pathways. Functional experiments showed that mutant Hnf1b cells had decreased tight junction integrity and altered cell morphology. These findings highlight the importance of HNF18 in regulating tight junction integrity and cell structure in the distal part of the nephron.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Lara W. Zeper, Edward R. Smith, Anique D. ter Braake, Paul T. Tinnemans, Jeroen H. F. de Baaij, Joost G. J. Hoenderop
Summary: Circulating calciprotein particles (CPP) have been identified as potential drivers of the calcification process in chronic kidney disease. This study compared CPP produced using different protocols in terms of particle morphology, composition, particle number, and in vitro calcification potency. The results showed that the composition of CPP and the method of quantification play a role in determining their calcification potency, and synthetic CPP are not comparable to endogenous CPP in terms of calcification propensity.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Review
Physiology
Minyu Zhang, Biyang Xiao, Xiaoqi Chen, Bingming Ou, Songtao Wang
Summary: Non-alcoholic fatty liver disease (NAFLD) is closely related to bile acid and gut microbiota disorders. Exercise plays an important role in maintaining the homeostasis of the enterohepatic circulation and the health of the host gut microbiota by regulating the composition and function of the bile acid pool in the enterohepatic axis. Exercise has been recommended as a first-line intervention for NAFLD, and regulating bile acids through exercise may be a promising treatment strategy.