Article
Medicine, Research & Experimental
Yong Wu, Huan Yang, Sujuan Xu, Ming Cheng, Jie Gu, Weichen Zhang, Shaojun Liu, Minmin Zhang
Summary: This study found that the AIM2 inflammasome plays a crucial role in aldosterone-induced renal injury, affecting ERS and fibrosis processes. Overactivation of AIM2 worsens the damage, while deficiency of AIM2 alleviates it.
Article
Peripheral Vascular Disease
Daigoro Hirohama, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Wakako Kawarazaki, Wataru Fujii, Shigeyoshi Oba, Shigeru Shibata, Takeshi Marumo, Toshiro Fujita
Summary: The study revealed that the activation of the Rac1-MR pathway contributes to the progression of DKD by causing hypertension and podocyte injury, highlighting MR antagonism and Rac1 inhibition as a novel strategy for DKD treatment.
Article
Biochemistry & Molecular Biology
Takumi Matsumoto, Shigehiro Doi, Ayumu Nakashima, Takeshi Ike, Kensuke Sasaki, Takao Masaki
Summary: This study investigated the role of the mineralocorticoid receptor (MR) in the progression of ischemia-reperfusion injury (IRI)-induced salt-sensitive hypertension. The results showed that MR upregulation may play a pivotal role in the development of salt-sensitive hypertension in response to salt overload or the activation of the renin-angiotensin-aldosterone system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Daiji Kawanami, Yuichi Takashi, Yoshimi Muta, Naoki Oda, Dai Nagata, Hiroyuki Takahashi, Makito Tanabe
Summary: Diabetic kidney disease is a major cause of end-stage kidney disease worldwide, with the mineralocorticoid receptor playing an important role in its development. Clinical studies have shown the benefits of MR antagonists for DKD, but concerns remain about their selectivity and hyperkalemia risks. New nonsteroidal MRAs, such as finerenone, have been developed with high selectivity and potent anti-inflammatory and anti-fibrotic properties, and a lower risk of hyperkalemia.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Jianzhong Li, Youjing Yang, Qianmin Li, Shuhui Wei, Yujia Zhou, Wangjianfei Yu, Lian Xue, Ling Zhou, Lei Shen, Guoyuan Lu, Ling Chen, Shasha Tao
Summary: This study reveals the mechanistic details of STAT6-mediated dysregulation of lipid metabolism in the progression of renal fibrosis, and provides a theoretical basis for improving the management of renal fibrosis caused by FAO dysregulation.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Benedikt Fels, Arne Beyer, Violeta Cazana-Perez, Teresa Giraldez, Juan F. Navarro-Gonzalez, Diego Alvarez de la Rosa, Franz Schaefer, Aysun K. Bayazit, Lukasz Obrycki, Bruno Ranchin, Johannes Holle, Uwe Querfeld, Kristina Kusche-Vihrog
Summary: This study found that chronic kidney disease disrupts endothelial mechanics, leading to endothelial dysfunction. The data showed that serum from CKD patients increased the stiffness of the endothelial glycocalyx and cortex, while decreasing the height of the glycocalyx. Furthermore, the study found that serum from hemodialysis patients increased the expression of MR and the mechanical stiffness of the endothelial cortex, an effect that could be reversed by MR and ENaC antagonists.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Arjun K. Pandey, Deepak L. Bhatt, Francesco Cosentino, Nikolaus Marx, Ori Rotstein, Bertram Pitt, Ambirash Pandey, Javed Butler, Subodh Verma
Summary: Despite current treatment options, patients with heart failure and chronic kidney disease (CKD) remain at high risk for adverse outcomes and disease progression. Non-steroidal mineralocorticoid receptor antagonists (MRAs) have emerged as a new dimension in the treatment of cardiorenal disease, offering unique pharmacological properties and benefits. These agents have anti-inflammatory, anti-remodelling, and anti-fibrotic effects in the heart, kidneys, and blood vessels. Although there are several non-steroidal MRAs in development, only esaxerenone and finerenone have been approved globally.
EUROPEAN HEART JOURNAL
(2022)
Review
Cardiac & Cardiovascular Systems
Rajiv Agarwal, Peter Kolkhof, George Bakris, Johann Bauersachs, Hermann Haller, Takashi Wada, Faiez Zannad
Summary: This review summarizes the development of mineralocorticoid receptor antagonists over the past 80 years, focusing on the mechanisms of action and advantages of nonsteroidal MRAs.
EUROPEAN HEART JOURNAL
(2021)
Review
Pharmacology & Pharmacy
Ulrich Kintscher, George L. Bakris, Peter Kolkhof
Summary: This review provides information on the molecular pharmacology and relevant clinical data of a new class of non-steroidal MRAs, discussing their cardiorenal outcomes. These compounds have an improved benefit-risk profile in treating cardiovascular diseases, and finerenone has a novel indication.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Guohui Qin, Shasha Liu, Jinyan Liu, Hongwei Hu, Li Yang, Qitai Zhao, Congcong Li, Bin Zhang, Yi Zhang
Summary: MDSCs gradually accumulate in esophageal cancer and targeting GPR84 enhances the efficacy of anti-PD-1 therapy by inhibiting immunosuppression. GPR84 is overexpressed on MDSCs and inhibits PD-L1 degradation, leading to immune suppression in CD8(+)T cells. G-CSF and GM-CSF induce GPR84 expression through STAT3/C/EBP beta signaling pathway. GPR84 antagonism combined with anti-PD-1 antibody enhances antitumor responses.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Yanhua Wang, Lauren M. LaRocque, Joseph A. Ruiz, Eva L. Rodriguez, Jeff M. Sands, Janet D. Klein
Summary: Hyponatremia is a water balance disorder due to abnormal renal diluting capacity. Vasopressin escape is a mechanism that limits the decrease in serum sodium concentration. Aldosterone and calcineurin play roles in regulating vasopressin escape through changes in UT-A1 and AQP2 proteins. Knockout mice lacking aldosterone synthase and rats treated with spironolactone or tacrolimus showed impaired vasopressin escape and altered protein abundances of UT-A1 and AQP2.
Article
Cell Biology
Estibaliz Castillero, Emmett Fitzpatrick, Samuel J. Keeney, Alex M. D'Angelo, Benjamin B. Pressly, Michael T. Simpson, Mangesh Kurade, W. Clinton Erwin, Vivian Moreno, Chiara Camillo, Halley J. Shukla, Vaishali V. Inamdar, Arbi Aghali, Juan B. Grau, Elisa Salvati, Itzhak Nissim, Lubica Rauova, Mark A. Oyama, Stanley J. Stachelek, Chase Brown, Abba M. Krieger, Robert J. Levy, Giovanni Ferrari
Summary: A decrease in serotonin transporter (SERT) activity is associated with accelerated progression of degenerative mitral valve (MV) regurgitation (MR). Selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype are linked to MV surgery at a younger age. Diminished SERT activity in MV interstitial cells (MVICs) contributes to MR pathophysiology through enhanced serotonin receptor (HTR) signaling.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Endocrinology & Metabolism
Ralph A. DeFronzo, George L. Bakris
Summary: Chronic kidney disease (CKD) is the most common cause of kidney failure in patients with type 2 diabetes and is a major contributor to the global burden of disease. However, current treatment options have limited effectiveness in slowing CKD progression and reducing cardiovascular events. Recent studies have shown that finerenone, a non-steroidal mineralocorticoid receptor antagonist, is an effective treatment for slowing CKD progression and providing cardiovascular protection in patients with type 2 diabetes.
DIABETES OBESITY & METABOLISM
(2022)
Article
Cell Biology
Andrew S. Terker, Yahua Zhang, Juan Pablo Arroyo, Shirong Cao, Suwan Wang, Xiaofeng Fan, Jerod S. Denton, Ming-Zhi Zhang, Raymond C. Harris
Summary: Inadequate potassium consumption is correlated with increased mortality and poor cardiovascular outcomes. This study demonstrates that potassium deficiency can directly cause kidney injury, and the effects are dependent on reduced blood potassium levels.
Article
Immunology
Randall C. Gunther, Vanthana Bharathi, Stephen D. Miles, Lauryn R. Tumey, Clare M. Schmedes, Kohei Tatsumi, Meagan D. Bridges, David Martinez, Stephanie A. Montgomery, Melinda A. Beck, Eric Camerer, Nigel Mackman, Silvio Antoniak
Summary: Global Par2 or myeloid cell deficiency, but not lung epithelial cell deficiency, was associated with reduced BALF inflammatory markers and reduced IAV-induced mortality in mice. This study suggests that PAR2 may be a therapeutic target to reduce IAV pathology.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pathology
Ana B. Nunez-Nescolarde, David J. Nikolic-Paterson, Alexander N. Combes
Summary: Kidney organoids and tubuloids are suitable models for studying kidney diseases and can help elucidate the pathogenic mechanisms, but their use in complex diseases is still in the early stages.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Editorial Material
Physiology
Patrick Ming-Kuen Tang, Haiyong Chen, Ying Tang, David J. Nikolic-Paterson, Hui Yao Lan
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Urology & Nephrology
Melissa S. Cheetham, Yeoungjee Cho, Rathika Krishnasamy, Arsh K. Jain, Neil Boudville, David W. Johnson, Louis L. Huang
Summary: Incremental peritoneal dialysis (PD) refers to lower than standard dose PD prescription, which has potential benefits like better preservation of residual kidney function and reduced risk of peritonitis. However, it may also lead to reduced solute clearance and fluid overload.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Cell Biology
James van der Wolde, Kotaro Haruhara, Victor G. Puelles, David Nikolic-Paterson, John F. Bertram, Luise A. Cullen-McEwen
Summary: This study investigated the progressive loss of podocytes during healthy aging and how the remaining podocytes respond to podocyte depletion at different ages. The results showed that podocyte number per glomerulus did not change in control mice during the examined time period but control mice at 18 months had the largest podocytes and the lowest podocyte density. Podocyte depletion at different ages resulted in different levels of albuminuria and glomerulosclerosis. In addition, the study found that the mTORC1-mediated podocyte hypertrophy played an important role in both physiological aging and adaptive settings.
CELL AND TISSUE RESEARCH
(2022)
Review
Endocrinology & Metabolism
Nikshay Karthigan, Siobhan Lockwood, Anthony White, Jun Yang, Morag J. Young
Summary: The mineralocorticoid receptor plays an important role in heart failure, but its treatment benefit is unclear for patients with preserved ejection fraction. Currently, there are no biomarkers available to predict treatment response, but finding such biomarkers is crucial for improving treatment efficacy and avoiding unnecessary side effects.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Jacqueline M. Ogier, Yujing Gao, Eileen M. Dunne, Michael A. Wilson, Sarath C. Ranganathan, Gregory H. Tesch, David JNikolic Paterson, Alain Dabdoub, Rachel A. Burt, Bryony A. Nayagam, Paul J. Lockhart
Summary: Aminoglycoside antibiotics can cause toxic effects on the sensory hair cells in the inner ear, leading to permanent hearing loss and vestibular impairment. This study investigates the potential of ASK1 inhibition as a novel strategy to prevent aminoglycoside ototoxicity, providing significant pre-clinical evidence.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Correction
Genetics & Heredity
Jacqueline M. Ogier, Yujing Gao, Eileen M. Dunne, Michael A. Wilson, Sarath C. Ranganathan, Gregory H. Tesch, David J. Nikolic Paterson, Alain Dabdoub, Rachel A. Burt, Bryony A. Nayagam, Paul J. Lockhart
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Endocrinology & Metabolism
Colin D. Clyne, Kevin P. Kusnadi, Alexander Cowcher, James Morgan, Jun Yang, Peter J. Fuller, Morag J. Young
Summary: The mineralocorticoid receptor (MR) is a ligand-activated transcription factor that regulates cardiorenal physiology and disease. The study evaluated the circadian protein TIMELESS as a selective regulator of MR transactivation and suggested that TIMELESS may contribute to MR transcriptional outputs via enhancing ER alpha inhibitory actions on MR transactivation.
JOURNAL OF MOLECULAR ENDOCRINOLOGY
(2023)
Article
Pediatrics
Yohei Ikezumi, Masatoshi Yoshikane, Tomomi Kondoh, Yuji Matsumoto, Naonori Kumagai, Masahiro Kaneko, Hiroya Hasegawa, Takeshi Yamada, Toshiaki Suzuki, David J. Nikolic-Paterson
Summary: This study showed that mizoribine can slow down the progression of kidney fibrosis in childhood IgA nephropathy by reducing the number of specific macrophage populations associated with fibrosis.
PEDIATRIC NEPHROLOGY
(2023)
Article
Urology & Nephrology
Jinhua Li, Xinli Qu, Chengnong Guan, Ning Luo, Huiting Chen, Andy Li, Hongjie Zhuang, Jiayi Yang, Hui Diao, Shuhan Zeng, Qing Wang, Jinjin Fan, Mengjie Jiang, Xiaoyan Bai, Zhiming Ye, Xiaoyun Jiang, Wei Chen, David J. Nikolic-Paterson, Xueqing Yu
Summary: Progressive fibrosis is a characteristic of chronic kidney disease, but effective treatments are lacking. The micropeptide regulator of b-oxidation (MOXI) is found to regulate kidney fibrosis. MOXI expression is up-regulated in human fibrotic kidney disease, and its deletion protects mice against fibrosis and inflammation. Antisense MOXI oligonucleotide treatment effectively reduces MOXI expression and protects against kidney fibrosis.
KIDNEY INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Jeff Yat-Fai Chung, Philip Chiu-Tsun Tang, Max Kam-Kwan Chan, Vivian Weiwen Xue, Xiao-Ru Huang, Calvin Sze-Hang Ng, Dongmei Zhang, Kam-Tong Leung, Chun-Kwok Wong, Tin-Lap Lee, Eric W-F Lam, David J. Nikolic-Paterson, Ka-Fai To, Hui-Yao Lan, Patrick Ming-Kuen Tang
Summary: In this study, the researchers found that phenotype and function of tumor-associated neutrophils (TANs) are influenced by the microenvironment, resulting in different impact on tumor development as N1 or N2 state. They discovered that Smad3 activation is negatively correlated with N2 state and patient survival in NSCLC patients. In preclinical lung cancer models, targeting Smad3 reprogrammed TANs to an antitumor state (N1), suppressing tumor growth. Mechanistically, Smad3 regulated the maturity of TANs and maintained the N2 state through controlling genes related to cell fate determination. Thus, the findings suggest that Smad3 signaling could be a therapeutic target for cancer immunotherapy.
NATURE COMMUNICATIONS
(2023)
Review
Endocrinology & Metabolism
Jun Yang, Morag J. Young, Timothy J. Cole, Peter J. Fuller
Summary: Primary aldosteronism, or Conn syndrome, is the most common endocrine cause of hypertension. It is associated with a higher risk of cardiovascular, metabolic, and renal diseases and leads to a lower quality of life compared to hypertension caused by other reasons. The multi-systemic effects of primary aldosteronism can be attributed to aldosterone-mediated activation of the mineralocorticoid receptor in various tissues. Recognizing primary aldosteronism as a multi-system disease with tissue-specific pathophysiology may result in more vigilant testing and earlier targeted interventions.
JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Urology & Nephrology
Melissa S. Cheetham, Yeoungjee Cho, Rathika Krishnasamy, Elasma Milanzi, Josephine Chow, Carmel Hawley, Jo-Anne Moodie, Matthew D. Jose, Robert MacGinley, Thu Nguyen, Suetonia C. Palmer, Rachael Walker, Jeffrey Wong, Arsh K. Jain, Neil Boudville, David W. Johnson, Louis L. Huang
Summary: The use of incremental PD is increasing in Australia and New Zealand and is not associated with patient harm.
PERITONEAL DIALYSIS INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Monica Kanki, Artika P. Nath, Ruidong Xiang, Stephanie Yiallourou, Peter J. Fuller, Timothy J. Cole, Rodrigo Canovas, Morag J. Young
Summary: Disrupted circadian rhythms have been found to be associated with an increased risk of hypertension and cardiovascular disease. This study reveals a U-shaped relationship between sleep length and SBP/DBP, and a positive association between poor sleep quality/night shift work and SBP/DBP.
NATURE COMMUNICATIONS
(2023)