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Article ; Online: YB-1: the Jekyll and Hyde of kidney disease?

Kantharidis, Phillip / Cooper, Mark E

2023 Volume 105, Issue 1, Page(s) 18–20

Abstract: Y-box-binding protein 1 is a well-described and important regulator of gene transcription, which is linked to various pathologic conditions, including inflammation and fibrosis of the kidney. The identification of a novel and protective crosstalk pathway ...

Abstract	Y-box-binding protein 1 is a well-described and important regulator of gene transcription, which is linked to various pathologic conditions, including inflammation and fibrosis of the kidney. The identification of a novel and protective crosstalk pathway between podocytes and tubular cells in the kidney with Y-box-binding protein 1 acting as a paracrine messenger sheds new light and provides novel opportunities for renoprotection.
MeSH term(s)	Humans ; Y-Box-Binding Protein 1 ; Kidney Diseases ; Kidney ; Epithelial Cells ; Inflammation
Chemical Substances	Y-Box-Binding Protein 1
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2023.10.020
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Article ; Online: Potential of Modulating Aldosterone Signaling and Mineralocorticoid Receptor with microRNAs to Attenuate Diabetic Kidney Disease.

Hagiwara, Shinji / Gohda, Tomohito / Kantharidis, Phillip / Okabe, Jun / Murakoshi, Maki / Suzuki, Yusuke

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Diabetic Kidney Disease (DKD) is a significant complication of diabetes and primary cause of end-stage renal disease globally. The exact mechanisms underlying DKD remain poorly understood, but multiple factors, including the renin-angiotensin-aldosterone ...

Abstract	Diabetic Kidney Disease (DKD) is a significant complication of diabetes and primary cause of end-stage renal disease globally. The exact mechanisms underlying DKD remain poorly understood, but multiple factors, including the renin-angiotensin-aldosterone system (RAAS), play a key role in its progression. Aldosterone, a mineralocorticoid steroid hormone, is one of the key components of RAAS and a potential mediator of renal damage and inflammation in DKD. miRNAs, small noncoding RNA molecules, have attracted interest due to their regulatory roles in numerous biological processes. These processes include aldosterone signaling and mineralocorticoid receptor (MR) expression. Numerous miRNAs have been recognized as crucial regulators of aldosterone signaling and MR expression. These miRNAs affect different aspects of the RAAS pathway and subsequent molecular processes, which impact sodium balance, ion transport, and fibrosis regulation. This review investigates the regulatory roles of particular miRNAs in modulating aldosterone signaling and MR activation, focusing on their impact on kidney injury, inflammation, and fibrosis. Understanding the complex interaction between miRNAs and the RAAS could lead to a new strategy to target aldosterone signaling and MR activation using miRNAs. This highlights the potential of miRNA-based interventions for DKD, with the aim of enhancing kidney outcomes in individuals with diabetes.
MeSH term(s)	Humans ; Aldosterone ; Diabetic Nephropathies/genetics ; Fibrosis ; Inflammation ; MicroRNAs/genetics ; Mineralocorticoids ; Receptors, Mineralocorticoid/genetics
Chemical Substances	Aldosterone (4964P6T9RB) ; MicroRNAs ; Mineralocorticoids ; Receptors, Mineralocorticoid
Language	English
Publishing date	2024-01-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25020869
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Article ; Online: Pro-resolving lipid mediators: regulators of inflammation, metabolism and kidney function.

Brennan, Eoin / Kantharidis, Phillip / Cooper, Mark E / Godson, Catherine

Nature reviews. Nephrology

2021 Volume 17, Issue 11, Page(s) 725–739

Abstract: Obesity, diabetes mellitus, hypertension and cardiovascular disease are risk factors for chronic kidney disease (CKD) and kidney failure. Chronic, low-grade inflammation is recognized as a major pathogenic mechanism that underlies the association between ...

Abstract	Obesity, diabetes mellitus, hypertension and cardiovascular disease are risk factors for chronic kidney disease (CKD) and kidney failure. Chronic, low-grade inflammation is recognized as a major pathogenic mechanism that underlies the association between CKD and obesity, impaired glucose tolerance, insulin resistance and diabetes, through interaction between resident and/or circulating immune cells with parenchymal cells. Thus, considerable interest exists in approaches that target inflammation as a strategy to manage CKD. The initial phase of the inflammatory response to injury or metabolic dysfunction reflects the release of pro-inflammatory mediators including peptides, lipids and cytokines, and the recruitment of leukocytes. In self-limiting inflammation, the evolving inflammatory response is coupled to distinct processes that promote the resolution of inflammation and restore homeostasis. The discovery of endogenously generated lipid mediators - specialized pro-resolving lipid mediators and branched fatty acid esters of hydroxy fatty acids - which promote the resolution of inflammation and attenuate the microvascular and macrovascular complications of obesity and diabetes mellitus highlights novel opportunities for potential therapeutic intervention through the targeting of pro-resolution, rather than anti-inflammatory pathways.
MeSH term(s)	Diabetes Mellitus/metabolism ; Diabetic Angiopathies/metabolism ; Diabetic Nephropathies/metabolism ; Humans ; Inflammation/metabolism ; Inflammation Mediators/metabolism ; Kidney/metabolism ; Lipid Metabolism ; Lipids ; Obesity/metabolism ; Renal Insufficiency, Chronic/metabolism
Chemical Substances	Inflammation Mediators ; Lipids
Language	English
Publishing date	2021-07-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/s41581-021-00454-y
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Article: Ameliorating diabetes-associated atherosclerosis and diabetic nephropathy through modulation of soluble guanylate cyclase.

Sharma, Arpeeta / Choi, Judy / Sim, Lachlan / Dey, Abhiroop / Mohan, Muthukumar / Kantharidis, Phillip / Dietz, Lisa / Sandner, Peter / de Haan, Judy B

Frontiers in cardiovascular medicine

2023 Volume 10, Page(s) 1220095

Abstract: Diabetes mellitus (DM) is an independent risk factor for micro- and macrovascular complications such as nephropathy and atherosclerosis respectively, which are the major causes of premature morbidity and mortality in Type 1 and Type 2 diabetic patients. ... ...

Abstract	Diabetes mellitus (DM) is an independent risk factor for micro- and macrovascular complications such as nephropathy and atherosclerosis respectively, which are the major causes of premature morbidity and mortality in Type 1 and Type 2 diabetic patients. Endothelial dysfunction is the critical first step of vascular disease and is characterized by reduced bioavailability of the essential endothelial vasodilator, nitric oxide (NO), coupled with an elevation in inflammation and oxidative stress. A novel pathway to bolster NO activity is to upregulate soluble guanylate cyclase (sGC), an enzyme responsible for mediating the protective actions of NO. Two classes of sGC modulators exist, activators and stimulators, with differing sensitivity to oxidative stress. In this study, we investigated the therapeutic effects of the sGC stimulator BAY 41-2272 (Bay 41) and the sGC activator BAY 60-2770 (Bay 60) on endpoints of atherosclerosis and renal disease as well as inflammation and oxidative stress in diabetic Apolipoprotein E knockout (ApoE-/-) mice. We hypothesized that under oxidative conditions known to accompany diabetes, sGC activation might be more efficacious than sGC stimulation in limiting diabetic vascular complications. We demonstrate that Bay 60 not only significantly decreased nitrotyrosine staining (
Language	English
Publishing date	2023-07-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2023.1220095
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Article: Potential Targeting of Renal Fibrosis in Diabetic Kidney Disease Using MicroRNAs.

Sakuma, Hiroko / Hagiwara, Shinji / Kantharidis, Phillip / Gohda, Tomohito / Suzuki, Yusuke

Frontiers in pharmacology

2020 Volume 11, Page(s) 587689

Abstract: Diabetic kidney disease (DKD) is a major health problem and one of the leading causes of end-stage renal disease worldwide. Despite recent advances, there exists an urgent need for the development of new treatments for DKD. DKD is characterized by the ... ...

Abstract	Diabetic kidney disease (DKD) is a major health problem and one of the leading causes of end-stage renal disease worldwide. Despite recent advances, there exists an urgent need for the development of new treatments for DKD. DKD is characterized by the excessive synthesis and deposition of extracellular matrix proteins in glomeruli and the tubulointerstitium, ultimately leading to glomerulosclerosis as well as interstitial fibrosis. Renal fibrosis is the final common pathway at the histological level leading to an end-stage renal failure. In fact, activation of the nuclear factor erythroid 2-related factor 2 pathway by bardoxolone methyl and inhibition of transforming growth factor beta signaling by pirfenidone have been assumed to be effective therapeutic targets for DKD, and various basic and clinical studies are currently ongoing. MicroRNAs (miRNAs) are endogenously produced small RNA molecules of 18-22 nucleotides in length, which act as posttranscriptional repressors of gene expression. Studies have demonstrated that several miRNAs contribute to renal fibrosis. In this review, we outline the potential of using miRNAs as an antifibrosis treatment strategy and discuss their clinical application in DKD.
Language	English
Publishing date	2020-11-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.587689
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Article ; Online: Specialized pro-resolving mediators in diabetes: novel therapeutic strategies.

Brennan, Eoin P / Mohan, Muthukumar / Andrews, Darrell / Bose, Madhura / Kantharidis, Phillip

Clinical science (London, England : 1979)

2019 Volume 133, Issue 21, Page(s) 2121–2141

Abstract: Diabetes mellitus (DM) is an important metabolic disorder characterized by persistent hyperglycemia resulting from inadequate production and secretion of insulin, impaired insulin action, or a combination of both. Genetic disorders and insulin receptor ... ...

Abstract	Diabetes mellitus (DM) is an important metabolic disorder characterized by persistent hyperglycemia resulting from inadequate production and secretion of insulin, impaired insulin action, or a combination of both. Genetic disorders and insulin receptor disorders, environmental factors, lifestyle choices and toxins are key factors that contribute to DM. While it is often referred to as a metabolic disorder, modern lifestyle choices and nutrient excess induce a state of systemic chronic inflammation that results in the increased production and secretion of inflammatory cytokines that contribute to DM. It is chronic hyperglycemia and the low-grade chronic-inflammation that underlies the development of microvascular and macrovascular complications leading to damage in a number of tissues and organs, including eyes, vasculature, heart, nerves, and kidneys. Improvements in the management of risk factors have been beneficial, including focus on intensified glycemic control, but most current approaches only slow disease progression. Even with recent studies employing SGLT2 inhibitors demonstrating protection against cardiovascular and kidney diseases, kidney function continues to decline in people with established diabetic kidney disease (DKD). Despite the many advances and a greatly improved understanding of the pathobiology of diabetes and its complications, there remains a major unmet need for more effective therapeutics to prevent and reverse the chronic complications of diabetes. More recently, there has been growing interest in the use of specialised pro-resolving mediators (SPMs) as an exciting therapeutic strategy to target diabetes and the chronic complications of diabetes.
MeSH term(s)	Diabetes Mellitus/classification ; Diabetes Mellitus/drug therapy ; Diabetic Angiopathies/drug therapy ; Diabetic Angiopathies/etiology ; Humans ; Molecular Targeted Therapy
Language	English
Publishing date	2019-11-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20190067
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Article ; Online: Therapeutic Potential of Lipoxin A

Fu, Ting / Mohan, Muthukumar / Brennan, Eoin P / Woodman, Owen L / Godson, Catherine / Kantharidis, Phillip / Ritchie, Rebecca H / Qin, Cheng Xue

ACS pharmacology & translational science

2020 Volume 3, Issue 1, Page(s) 43–55

Abstract: Several studies have shown that failure to resolve inflammation may contribute to the progression of many chronic inflammatory disorders. It has been suggested targeting the resolution of inflammation might be a novel therapeutic approach for chronic ... ...

Abstract	Several studies have shown that failure to resolve inflammation may contribute to the progression of many chronic inflammatory disorders. It has been suggested targeting the resolution of inflammation might be a novel therapeutic approach for chronic inflammatory diseases, including inflammatory bowel disease, diabetic complications, and cardiometabolic disease. Lipoxins [LXs] are a class of endogenously generated mediators that promote the resolution of inflammation. Biological actions of LXs include inhibition of neutrophil infiltration, promotion of macrophage polarization, increase of macrophage efferocytosis, and restoration of tissue homeostasis. Recently, several studies have demonstrated that LXs and synthetic analogues protect tissues from acute and chronic inflammation. The mechanism includes down-regulation of pro-inflammatory cytokines and chemokines (e.g., interleukin-1β and tumor necrosis factor-α), inhibition of the activation of the master pro-inflammatory pathway (e.g., nuclear factor κ-light-chain-enhancer of activated B cells pathway) and increased release of the pro-resolving cytokines (e.g., interleukin-10). Three generations of LXs analogues are well described in the literature, and more recently a fourth generation has been generated that appears to show enhanced potency. In this review, we will briefly discuss the potential therapeutic opportunity provided by lipoxin A
Language	English
Publishing date	2020-01-17
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2575-9108
ISSN (online)	2575-9108
DOI	10.1021/acsptsci.9b00097
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Article: The Use of Targeted Next Generation Sequencing to Explore Candidate Regulators of TGF-β1's Impact on Kidney Cells.

Wang, Bo / Ji, Guanyu / Naeem, Haroon / Wang, Junwen / Kantharidis, Phillip / Powell, David / Ricardo, Sharon D

Frontiers in physiology

2018 Volume 9, Page(s) 1755

Abstract: Aims/Hypothesis: ...

Abstract	Aims/Hypothesis:
Language	English
Publishing date	2018-12-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2018.01755
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Article ; Online: Where are we in diabetic nephropathy: microRNAs and biomarkers?

McClelland, Aaron / Hagiwara, Shinji / Kantharidis, Phillip

Current opinion in nephrology and hypertension

2014 Volume 23, Issue 1, Page(s) 80–86

Abstract: Purpose of review: Several factors are now known to contribute to the development and progression of nephropathy, particularly in diabetes. In recent times, there has been surge of interest in the role of small noncoding RNA, with several reports ... ...

Abstract	Purpose of review: Several factors are now known to contribute to the development and progression of nephropathy, particularly in diabetes. In recent times, there has been surge of interest in the role of small noncoding RNA, with several reports focusing on the effects of microRNAs on their target genes that are of relevance to nephropathy. This review focuses on recent progress in this field. Recent findings: The list of microRNAs that have been identified to play a role in nephropathy continues to grow. Of particular interest is the fact that most microRNAs that are implicated in nephropathy are regulated by the profibrotic factor, transforming growth factor-β. Additionally, some recent studies have used the presence of microRNAs in biofluids as a source of potential biomarkers for many diseases, particularly in diabetic nephropathy. Summary: MicroRNAs hold much promise given their novelty, promiscuity and involvement in many biological and pathological processes. There are promising early signs of their potential as biomarkers as well as therapeutic targets.
MeSH term(s)	Animals ; Diabetic Nephropathies/diagnosis ; Diabetic Nephropathies/genetics ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/therapy ; Genetic Markers ; Genetic Therapy/methods ; Humans ; Kidney/metabolism ; MicroRNAs/metabolism ; MicroRNAs/therapeutic use ; Predictive Value of Tests ; Prognosis ; Renin-Angiotensin System
Chemical Substances	Genetic Markers ; MicroRNAs
Language	English
Publishing date	2014-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/01.mnh.0000437612.50040.ae
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Zs.A 3686: Show issues

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Article ; Online: microRNA in the development of diabetic complications.

McClelland, Aaron D / Kantharidis, Phillip

Clinical science (London, England : 1979)

2014 Volume 126, Issue 2, Page(s) 95–110

Abstract: Today's world population is currently faced with a new type of non-transmissible pandemic: obesity. This lifestyle-related condition is driving the emergence of the diabetes pandemic through the development of low-level chronic inflammation. In recent ... ...

Abstract	Today's world population is currently faced with a new type of non-transmissible pandemic: obesity. This lifestyle-related condition is driving the emergence of the diabetes pandemic through the development of low-level chronic inflammation. In recent years, a novel class of non-coding RNA, microRNA (miRNA), have emerged as being important regulators of numerous biological functions. Among these functions are basic maintenance of cell signalling and tissue architecture. Disruption of miRNA levels can contribute not only to the development of the chronic inflammation observed in obese diabetics, but also the development of both pancreatic β-cell dysfunction and loss, along with insulin resistance in metabolic tissues. These primary events set the scene for dysfunction of other tissues, including the retina, kidney, peripheral nerves, heart and the vasculature as a whole. Here, miRNAs again play a deterministic role in the development of a range of diseases collectively termed diabetic complications. Disturbances in miRNA levels appear to be reflected in the serum of patients and this may prove to be diagnostic in patients prior to clinical manifestation of disease, thus improving management of diabetes and its associated complications. Not only are miRNAs displaying promise as an early biomarker for disease, but a number of these miRNAs are displaying therapeutic potential with several in pre-clinical development. The present review aims to highlight our current understanding of miRNAs and their interaction with inflammatory signalling in the development and progression of diabetes and its complications. Utilization of miRNAs as biomarkers and therapeutic targets will also be considered.
MeSH term(s)	Adipose Tissue/metabolism ; Animals ; Atherosclerosis/etiology ; Biomarkers/blood ; Blood Glucose/metabolism ; Cardiomyopathies/etiology ; Diabetes Complications/drug therapy ; Diabetes Complications/etiology ; Diabetes Complications/genetics ; Diabetic Nephropathies/physiopathology ; Diabetic Retinopathy/physiopathology ; Humans ; Inflammation/complications ; Insulin Resistance/genetics ; Liver/metabolism ; MicroRNAs/physiology ; MicroRNAs/therapeutic use ; Muscle, Skeletal/metabolism ; Obesity/complications ; Rats ; Signal Transduction/genetics
Chemical Substances	Biomarkers ; Blood Glucose ; MicroRNAs
Language	English
Publishing date	2014-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20130079
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