Article
Biochemistry & Molecular Biology
Federica Petrillo, Dmitry Chernyakov, Cristina Esteva-Font, Soren B. Poulsen, Bayram Edemir, Robert A. Fenton
Summary: Water homeostasis is regulated by the kidneys through urine concentration. The antidiuretic hormone AVP enhances water reabsorption through binding to V2R in the kidney. ELF5 and NFAT5 are transcription factors that regulate Aqp2 expression and play important roles in renal water handling. The absence of NFAT5 leads to nephrogenic diabetes insipidus.
Article
Physiology
Sua Kim, Chor Ho Jo, Gheun-Ho Kim
Summary: This study demonstrates that antipsychotic drugs like haloperidol, sertraline, and carbamazepine can induce nephrogenic syndrome of inappropriate antidiuresis by upregulating vasopressin-2 receptor and aquaporin-2 (AQP2) through cAMP/PKA signaling. Additionally, these drugs also increase AQP2 protein abundance through dephosphorylation at Ser(261) and enhanced transcription.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Physiology
Hsiu-Hui Yang, Shih-Han Su, Cheng-Hsuan Ho, Ai-Hsin Yeh, Yi-Jiun Lin, Ming-Jiun Yu
Summary: The expression of the water channel protein AQP2 is regulated by the glucocorticoid receptor and the pituitary hormone vasopressin. Transcriptomic comparison revealed positive and negative regulatory pathways maintained by the glucocorticoid receptor for the vasopressin-induced Aqp2 gene expression.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Physiology
Cheng-Hsuan Ho, Hsiu-Hui Yang, Shih-Han Su, Ai-Hsin Yeh, Ming-Jiun Yu
Summary: Vasopressin regulates the water permeability of kidney collecting ducts by inducing the expression of aquaporin-2 through the interaction between alpha-actinin 4 and glucocorticoid receptor. This mechanism provides an important pathway for the regulation of water reabsorption in the kidney collecting ducts.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Physiology
Euijung Park, Chin-Rang Yang, Viswanathan Raghuram, Venkatesh Deshpande, Arnab Datta, Brian G. Poll, Kirby T. Leo, Hiroaki Kikuchi, Lihe Chen, Chung-Lin Chou, Mark A. Knepper
Summary: Vasopressin regulates renal water excretion by controlling aquaporin-2 (AQP2) through phosphorylation changes in collecting duct cells. This review identifies 51 vasopressin-regulated phosphorylation sites in 45 proteins and emphasizes the importance of these sites in AQP2 regulation. The study provides web pages listing the phosphorylation sites and functions of the targeted phosphoproteins, suggesting a central role for protein kinase A (PKA) in vasopressin signaling. Other kinases, such as ERK1/2, Camkk2, Cdk18, Erbb3, Mink1, and Src, may also be involved in vasopressin-induced phosphorylation changes. Mapping the regulated phosphoproteins to various processes offers opportunities for future studies on vasopressin-mediated control of AQP2.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tomoaki Takata, Shintaro Hamada, Yukari Mae, Takuji Iyama, Ryohei Ogihara, Misako Seno, Kazuomi Nakamura, Miki Takata, Takaaki Sugihara, Hajime Isomoto
Summary: This study found that the production of uromodulin is regulated during water deprivation in vivo, and it activates AQP2 by suppressing endocytosis, enhancing its apical trafficking. This finding provides new insights into the cross-talk between the thick ascending limb and the collecting duct, and suggests that modulation of uromodulin may be a promising approach for diuresis and hypertension treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Bjorn Reusch, Malte P. Bartram, Claudia Dafinger, Nicolas Palacio-Escat, Andrea Wenzel, Robert A. Fenton, Julio Saez-Rodriguez, Bernhard Schermer, Thomas Benzing, Janine Altmueller, Bodo B. Beck, Markus M. Rinschen
Summary: Mutations in the MAGED2 gene can cause Bartter Syndrome type 5, characterized by the loss of urinary concentration capability and large urine volumes. The MAGED2 gene is expressed in mouse embryonic kidneys and its knockdown affects protein phosphorylation in kidney cells. This study provides insights into the role of MAGED2 in cellular signalling and potential implications for development and disease.
JOURNAL OF PROTEOMICS
(2022)
Article
Medicine, Research & Experimental
Juan Pablo Arroyo, Andrew S. Terker, Yvonne Zuchowski, Jason A. Watts, Fabian Bock, Cameron Meyer, Wentian Luo, Meghan E. Kapp, Edward R. Gould, Adam X. Miranda, Joshua Carty, Ming Jiang, Roberto M. Vanacore, Elizabeth Hammock, Matthew H. Wilson, Roy Zent, Mingzhi Zhang, Gautam Bhave, Raymond C. Harris
Summary: Research has found that vasopressin can be produced in the kidneys, specifically in the tubular epithelial cells of mouse and human kidneys. This kidney-derived vasopressin is biologically active and regulated by hypertonic conditions and water restriction.
Article
Pharmacology & Pharmacy
Arnab Datta, Chin-Rang Yang, Karim Salhadar, Euijung Park, Chung-Lin Chou, Viswanathan Raghuram, Mark A. Knepper
Summary: This study systematically analyzed vasopressin-induced phosphorylation changes and identified at least six downstream protein kinases that are regulated by vasopressin, providing important insights for future research.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Swapnalee Sarmah, Matthew R. Hawkins, Priyadharshini Manikandan, Mark Farrell, James A. Marrs
Summary: The E26 transformation specific (ETS) family transcription factor ELF3 plays a critical role in the development of epidermal, mesenchymal, and neural tissues in zebrafish. Loss of Elf3 function leads to defects in notochord, craniofacial cartilage, and fin development, as well as neural abnormalities. Disruption of extracellular matrix organization and dysregulation of genes encoding ECM proteins and matrix metalloproteases (MMP) may contribute to the observed phenotypes in Elf3-morphants.
Article
Multidisciplinary Sciences
Marianna Ranieri, Annarita Di Mise, Mariangela Centrone, Mariagrazia D'Agostino, Stine Julie Tingskov, Maria Venneri, Tommaso Pellegrino, Graziana Difonzo, Francesco Caponio, Rikke Norregaard, Giovanna Valenti, Grazia Tamma
Summary: The Olive Leaf Extract (OLE) has been shown to prevent the translocation of AQP2 induced by vasopressin, decrease the osmotic water permeability coefficient, and stimulate the Calcium Sensing Receptor (CaSR) in renal cells. In vivo experiments further demonstrated that OLE increases CaSR mRNA expression, decreases AQP2 mRNA expression, and increases miRNA-137 targeting AQP2, suggesting its potential to attenuate disorders involving abnormal CaSR signaling and renal water reabsorption.
SCIENTIFIC REPORTS
(2021)
Article
Physiology
Chuanming Xu, Yanting Chen, Nirupama Ramkumar, Chang-Jiang Zou, Curt D. Sigmund, Tianxin Yang
Summary: This study investigates the role of intrarenal RAAS in potassium homeostasis, specifically focusing on the action of renin in the collecting duct. The study found that mice with renal-specific deletion of renin had impaired potassium excretion and elevated plasma potassium levels when fed a high potassium diet. Additionally, the expression of intrarenal aldosterone and related proteins were also decreased.
Article
Cell Biology
Fabian Bock, Bertha C. Elias, Xinyu Dong, Diptiben Parekh, Glenda Mernaugh, Olga M. Viquez, Anjana Hassan, Venkateswara Rao Amara, Jiageng Liu, Kyle L. Brown, Andrew S. Terker, Manuel Chiusa, Leslie S. Gewin, Agnes B. Fogo, Cord H. Brakebusch, Ambra Pozzi, Roy Zent
Summary: The study demonstrates that Rac1 is not essential for epithelial branching morphogenesis during kidney collecting duct development, but plays a crucial role in maintaining epithelial integrity, polarity, and function by Arp2/3-dependent cytoskeletal branching. This function of Rac1 involves restricting actomyosin activity. Despite a mild developmental phenotype in mice with selectively deleting Rac1 at the initiation of UB development, aging leads to disruption of epithelial integrity and function in the collecting duct, which is reversible with direct myosin II inhibition. Additionally, Rac1 controls lateral membrane height and overall epithelial morphology by restricting actomyosin and promoting CD epithelial integrity.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Alba Ferre, Francois Chauvigne, Magdalena Gozdowska, Ewa Kulczykowska, Roderick Nigel Finn, Joan Cerda
Summary: The neurohypophysial and paracrine vasopressinergic systems regulate the trafficking of Aqp1ab-type paralogs via a common AVP-AVPR2AA-PKA pathway to avoid competitive occupancy of the same plasma membrane space and maximize water influx during oocyte hydration in marine teleosts.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hyo-Ju Jang, Hye-Jeong Park, Hong Seok Choi, Hyun Jun Jung, Tae-Hwan Kwon
Summary: This study aimed to establish mpkCCDc14 cells constitutively expressing V2R and AQP2 via CRISPR/Cas9-mediated genome engineering technology. The results showed that these cells had higher abundance of AQP2 protein in the absence of stimulation and exhibited normal response to dDAVP stimulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Medicine, General & Internal
Yung-Ho Hsu, Shuei-Liong Lin
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2022)
Article
Chemistry, Multidisciplinary
Hui-Teng Cheng, Hsi-Chien Huang, Tsung-Ying Lee, Yu-Hui Liao, Yi-Hua Sheng, Pei-Ru Jin, Kuan-Wei Huang, Ling-Hsuan Chen, Yi-Ting Chen, Zi-Yan Liu, Tzu-Chieh Lin, Hsueh-Cheng Wang, Cheng-Han Chao, I. Pu Juang, Chi-Ting Su, Kuo-How Huang, Shuei-Liong Lin, Jane Wang, Yun-Chieh Sung, Yunching Chen
Summary: The study demonstrates the therapeutic potential of utilizing nanotechnology-based drug carriers to target myofibroblasts and deliver therapeutic cargo specifically to fibrotic kidneys. This approach shows significant improvement in reducing renal fibrosis and systemic toxicity.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Yu-Syuan Wei, Hui-Ping Cheng, Ching-Ho Wu, Yen-Chen Chang, Ruo-Wei Lin, Yu-Ting Hsu, Yi-Ting Chen, Shuei-Liong Lin, Su-Yi Tsai, Shinn-Chih Wu, Pei-Shiue Tsai
Summary: Peritoneal dialysis is a renal replacement therapy, but long-term complications can compromise its effectiveness. Using a pig model, researchers found that disruption of the cell cytoskeleton could lead to peritoneal dysfunction and PD failure.
Review
Biochemistry & Molecular Biology
Yu-Hui Hung, Tai-Shuan Lai, Mohamed Belmouaz, Ya-Chun Tu, Chun-Fu Lai, Shuei-Liong Lin, Yung-Ming Chen
Summary: Studies have shown that MCO membranes are superior to standard high flux membranes in clearing middle molecular weight uremic toxins in hemodialysis. Meta-analysis results indicate significantly higher reduction ratio of serum β2M, κFLC, and λFLC in the MCO group. However, the use of MCO membranes may result in albumin loss, which should be monitored.
Article
Urology & Nephrology
Fan-Chi Chang, Chia-Hao Liu, An-Jie Luo, Thomas Tao-Min Huang, Ming-Hsuan Tsai, Yu-Jhen Chen, Chun-Fu Lai, Chih-Kang Chiang, Tzu-Hung Lin, Wen-Chih Chiang, Yung-Ming Chen, Tzong-Shinn Chu, Shuei-Liong Lin
Summary: Plasma levels of angiopoietin-2 are elevated in patients with chronic kidney disease (CKD), and this increase is associated with the development of kidney failure. Overexpression of angiopoietin-1 in mouse models of progressive kidney disease attenuates macrophage infiltration, endothelial cell apoptosis, microvascular rarefaction, and fibrosis. Additionally, an angiopoietin-2 inhibitor has inhibitory effects on macrophage infiltration, microvascular rarefaction, and fibrosis in these models.
KIDNEY INTERNATIONAL
(2022)
Article
Urology & Nephrology
Jeng-Wei Chen, Hsun-Yi Fu, Ing-Heng Hii, Hsien-Wei Tseng, Po-Ya Chang, Chin-Hao Chang, Yih-Sharng Chen, Ron -Bin Hsu, I-Hui Wu, Yung -Ming Chen, Tzong-Shinn Chu, Kuan-Yu Hung, Shuei-Liong Lin, Kwan-Dun Wu, Chih-Yang Chan
Summary: The study aimed to investigate the effectiveness of postoperative handgrip exercises (HGEs) in promoting the maturation of arteriovenous wrist fistula. 119 patients aged 20 to 80 with wrist arteriovenous fistulas were randomly assigned to three groups: basic HGE program (group A), advanced program (group B), or advanced plus upper arm banding program (group C). Ultrasonographic evaluation was used to assess the diameter and flow at different follow-up time points. There were no significant differences among the HGE groups in terms of the diameter, blood flow, and clinical use of fistulas.
KIDNEY INTERNATIONAL REPORTS
(2023)
Article
Medicine, General & Internal
Chun-Fu Lai, Jung-Hua Liu, Li-Jung Tseng, Chun-Hao Tsao, Nai-Kuan Chou, Shuei-Liong Lin, Yung-Ming Chen, Vin-Cent Wu
Summary: This study used unsupervised consensus clustering to investigate the heterogeneity in dialysis-requiring sepsis-associated acute kidney injury (SA-AKI) patients. Three sub-phenotypes were identified based on 23 clinical variables, which exhibited distinct clinical manifestations at the initiation of renal replacement therapy. Among them, sub-phenotype 1, characterized by younger age, lower Charlson Comorbidity Index, higher baseline estimated glomerular filtration rate but higher severity of acute illness, had a higher risk of death and a lower probability of being free of dialysis compared to sub-phenotype 3.
ANNALS OF MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Chun -Ting Yeh, Shih-Che Weng, Po-Nien Tsao, Shin -Hong Shiao
Summary: Binding immunoglobulin protein (BiP) plays a crucial role in both dengue virus replication and mosquito reproduction. Silencing BiP expression inhibits viral replication and reduces mosquito fertility and fecundity.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2023)
Article
Medicine, General & Internal
Zhi-Ye Yu, Tai-Shuan Lai, Shao-Yu Yang, Shih- Chen, Mei-Jun Lai, Chun-Min Kang, Yu-Tsung Huang, Yi-Ting Chen, Po-Ren Hsueh, Yung-Ming Chen, Shuei-Liong Lin
Summary: Patients on peritoneal dialysis (PD) had fewer adverse events after COVID-19 vaccination compared to volunteers. PD patients had lower antibody concentrations compared to volunteers, but the levels increased after the second dose of vaccination. The mRNA-1273 vaccine induced a higher antibody and T cell response than the ChAdOx1-S vaccine in PD patients.
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2023)
Article
Medicine, General & Internal
Hsiao-Mei Tsao, Tai-Shuan Lai, Yi-Cheng Chang, Chia-Ni Hsiung, Yu-Hsiang Chou, Vin -Cent Wu, Shuei-Liong Lin, Yung-Ming Chen
Summary: This study aimed to evaluate the association between serum urate and the risk of incident CKD, and to assess whether serum urate plays a causal role in CKD. The results showed that each mg/dL increase in serum urate was associated with a 15% higher risk of incident CKD. However, Mendelian randomization analyses failed to provide evidence that serum urate had a causal effect on CKD in the East Asian population.
MAYO CLINIC PROCEEDINGS
(2023)
Article
Pharmacology & Pharmacy
Yi-Chih Lin, Hsiao-Mei Tsao, Tai-Shuan Lai, Yi-Ting Chen, Yu-Hsiang Chou, Shuei-Liong Lin, Yung-Ming Chen, Kuan-Yu Hung, Yu-Kang Tu
Summary: The use of lipid-lowering drugs in patients with advanced chronic kidney disease and dyslipidemia can reduce the risk of end-stage kidney disease and major adverse cardiovascular events.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Chemistry, Medicinal
Wei-Chieh Yu, Tsung-Yu Yeh, Chih-Hung Ye, Patrick Chun Theng Chong, Yi-Hsun Ho, Dorothy Kazuno So, Kah Yi Yap, Guan-Ru Peng, Chi-Hsuan Shao, Ajit Dhananjay Jagtap, Ji-Wang Chern, Chen-Si Lin, Shau-Ping Lin, Shuei-Liong Lin, Shu-Han Yu, Chao-Wu Yu
Summary: Idiopathic pulmonary fibrosis is a difficult-to-control, incurable disease that can lead to pulmonary deterioration. The use of pan-histone deacetylase inhibitors has shown potential for reducing pulmonary fibrosis, but with off-target effects. This study aims to discover selective HDAC inhibitors for mitigating TGF-β-induced pulmonary fibrosis through a two-stage screening platform. The platform successfully identified two potential leads, J27644 (15) and 20, which can accelerate the development of HDAC inhibitors and reduce the cost.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Hsiao-Mei Tsao, Tai-Shuan Lai, Yu-Hsiang Chou, Shuei-Liong Lin, Yung-Ming Chen
Summary: This study investigated the changes in CKD-related biomarkers in patients with different trajectories of GFR decline. Eight out of 15 biomarkers showed distinct patterns among the trajectory groups. Those with a more rapid decline in GFR exhibited higher levels of blood urea nitrogen and urine protein-creatinine ratio, and a more rapid decline in hemoglobin and platelet counts. Lower levels of albumin and potassium, and higher levels of mean corpuscular hemoglobin concentration and white blood cell were associated with accelerated GFR decline. The albumin level in the group with accelerated GFR decline fell below the normal range.
THERAPEUTIC ADVANCES IN CHRONIC DISEASE
(2023)
Review
Urology & Nephrology
Yu-Hsiang Chou, Szu-Yu Pan, Shuei-Liong Lin
Summary: Anemia in patients with chronic kidney disease (CKD) is often caused by insufficient production of erythropoietin. While recombinant human erythropoietin-related products have been used to increase hemoglobin levels, safety concerns, such as cardiovascular events and cancer progression, have been raised. Prolyl hydroxylase domain (PHD) enzyme inhibitors have emerged as a new therapeutic option for anemia in CKD. These oral inhibitors have shown noninferior effect on erythropoiesis and improved functional iron deficiency in clinical trials. However, their pleotropic effects, including angiogenesis and metabolic changes, raise concerns about potential adverse effects such as fibrosis, inflammation, and tumor growth. Further studies are needed to confirm the safety and efficacy of PHD inhibitors.
KIDNEY RESEARCH AND CLINICAL PRACTICE
(2023)
Article
Urology & Nephrology
Yu-Hsiang Chou, Tai-Shuan Lai, Yi-Chih Lin, Wen-Chih Chiang, Tzong-Shinn Chu, Shuei-Liong Lin, Yung-Ming Chen
Summary: Older adults with chronic kidney disease (CKD) may experience accelerated progression of the disease due to acute kidney injury (AKI), despite old age being considered a positive modifier of CKD. This study aimed to investigate this paradoxical interaction and identify age-specific predictors for end-stage kidney disease (ESKD). The results showed that older adults with CKD had a slower decline rate of estimated glomerular filtration rate (eGFR) but were more likely to develop ESKD following AKI episodes. Therefore, preventing AKI to prevent accelerated initiation of renal replacement therapy in elderly patients with pre-existing CKD is necessary.