A5087666649- Chronic Kidney Disease and Diabetes
- Renal Diseases and Glomerulopathies
- Acute Kidney Injury Research
- Mast cells and histamine
- Drug-Induced Hepatotoxicity and Protection
- Melanoma and MAPK Pathways
- Renal Transplantation Outcomes and Treatments
- Genomics, phytochemicals, and oxidative stress
- Redox biology and oxidative stress
- Sulfur Compounds in Biology
- Renin-Angiotensin System Studies
- Nephrotoxicity and Medicinal Plants
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adrenal Hormones and Disorders
- Organ Transplantation Techniques and Outcomes
- Kidney Stones and Urolithiasis Treatments
- Immune cells in cancer
- Cell Adhesion Molecules Research
- Ureteral procedures and complications
- Growth Hormone and Insulin-like Growth Factors
- Cardiac Ischemia and Reperfusion
- Diabetes Treatment and Management
- Hormonal Regulation and Hypertension
- Ion Transport and Channel Regulation
- Blood Coagulation and Thrombosis Mechanisms
Monash University
2014-2024
Monash Medical Centre
2015-2024
Monash Health
2008-2024
Shaare Zedek Medical Center
2020-2022
St. Michael's Hospital
2022
Ben-Gurion University of the Negev
2012-2017
National Yang Ming Chiao Tung University
2015
Taipei Veterans General Hospital
2015
University of Otago
2004-2005
// Shuang Wang 1, * , Xiao-Ming Meng Yee-Yung Ng 2, Frank Y. Ma 3 Zhou 1 Yang Zhang Chen Xiao-Ru Huang Jun Xiao Ying-Ying Shuk-Man Ka Yong-Jiang Tang Arthur C.K. Chung Ka-Fai To David J. Nikolic-Paterson Hui-Yao Lan Li Shing Institute of Health Sciences, Departments Medicine and Therapeutics, Chemical Pathology, Anatomical Cellular The Chinese University Hong Kong, Kong SAR, China 2 Division Nephrology, Department Medicine, Clinical Taipei Veterans General Hospital, National Ming University,...
Renal fibrosis and tubular apoptosis are common mechanisms of progressive kidney disease. In vitro studies have implicated the c-Jun amino-terminal kinase (JNK) pathway in these processes. Both major JNK isoforms, JNK1 JNK2, expressed kidney, but their relative contribution to signaling is unknown. This study investigated role renal unilateral ureteral obstruction model using two different approaches: (1) Mice that were deficient either or JNK2 (2) a specific inhibitor all CC-401. Western...
Oxidative stress is an underlying component of acute and chronic kidney disease. Apoptosis signal–regulating kinase 1 (ASK1) a widely expressed redox-sensitive serine threonine that activates p38 c-Jun N-terminal (JNK) mitogen-activated protein kinases, induces apoptotic, inflammatory, fibrotic signaling in settings oxidative stress. We describe the discovery characterization potent selective small-molecule inhibitor ASK1, GS-444217, demonstrate therapeutic potential ASK1 inhibition to...
Stress-activated kinases p38 MAPK and JNK promote renal fibrosis; however, how the pathways by which these are activated in kidney disease remain poorly defined. Apoptosis signal-regulating kinase 1 (ASK1/MAPKKK5) is a member of MAPKKK family that can induce activation JNK. The present study examined whether ASK1 induces p38/JNK fibrosis unilateral ureteric obstruction (UUO) using wild-type (WT) Ask1-deficient (Ask1(-/-)) mice. Basal WT kidneys was increased three- to fivefold day 7 UUO mice...
Abstract Context Bilateral adrenal hemorrhage is a rare condition with potentially life-threatening consequences such as acute insufficiency. Early axis testing, well directed imaging, crucial for immediate diagnosis and treatment. Coronavirus disease 2019 (COVID-19) has been associated coagulopathy thromboembolic events. Case description A 66-year-old woman presented COVID-19 infection primary insufficiency due to bilateral (BAH). She also had renal vein thrombosis. Her past medical history...
Activation of c-Jun amino kinase (JNK), p38 mitogen-activated protein (MAPK), and the transcription factor nuclear factor-κB (NF-κB) drives renal inflammation fibrosis. However, upstream MAP (MAP3K) enzyme(s) that activate these pathways in kidney disease are unknown. We determined role one candidate MAP3K enzyme, transforming growth factor-β1-activated kinase-1 (TAK1/ MAP3K7), activation JNK, p38, NF-κB obstructed using conditional gene deletion adult mice, assessed potential protective...
p38 mitogen-activated protein kinase (MAPK) signaling promotes diabetic kidney injury. Apoptosis signal-regulating (ASK)1 is one of the upstream kinases in MAPK-signaling pathway, which activated by inflammation and oxidative stress, suggesting a possible role for ASK1 nephropathy. In this study, we examined whether selective inhibitor can prevent induction progression nephropathy mice. Diabetes was induced hypertensive endothelial nitric oxide synthase (Nos3)-deficient mice five low-dose...
The ability of macrophages to cause acute inflammatory glomerular injury is well-established; however, the role in fibrotic phase chronic kidney disease remains poorly understood. This study examined (days 14 35) established crescentic glomerulonephritis. Nephrotoxic serum nephritis (NTN) was induced groups eight Wistar-Kyoto rats that were given a selective c-fms kinase inhibitor, fms-I, or vehicle alone from day until being killed on 35. Rats NTN had pronounced macrophage infiltration with...
Background. IL-1β has the potential to promote progressive renal disease by effects on macrophage recruitment and activation or mediated through tubular cell transforming growth factor (TGF)-β production, previously demonstrated in vitro.
Depletion and adoptive transfer studies have demonstrated that macrophages induce glomerular lesions in experimental anti-glomerular basement membrane (anti-GBM) glomerulonephritis. However, there is no current therapeutic strategy can rapidly selectively remove these cells from the glomerulus order to halt disease development. This study examined whether inhibition of receptor for macrophage colony-stimulating factor (known as c-fms), which expressed by monocyte/macrophages, eliminate...
Clinical and experimental studies have shown that mineralocorticoid receptor (MR) antagonists substantially reduce kidney injury. However, the specific cellular targets mechanisms by which MR protect against injury must be identified. We used conditional gene deletion of signaling in myeloid cells (MR(flox/flox) LysM(Cre) mice; MyMRKO) or podocytes Pod(Cre) PodMRKO) to establish role these cell types development mouse GN. Accelerated anti-glomerular basement membrane GN was examined groups...
Abstract Activation of p38 mitogen‐activated protein kinase ( MAPK ) and c‐Jun amino terminal JNK is prominent in human crescentic glomerulonephritis. inhibitors suppress disease animal models; however, the upstream mechanisms inducing activation these kinases glomerulonephritis are unknown. We investigated hypothesis that apoptosis signal‐regulating 1 ASK 1/ MAP 3K5) promote p38/ renal injury models nephrotoxic serum nephritis NTN ); acute glomerular SD rats, WKY rats. Treatment with...
The hypothalamic neuroendocrine dopaminergic (NEDA) neurons are crucial in regulating prolactin secretion from the anterior pituitary. Rising concentrations stimulate these to secrete dopamine, which acts via pituitary portal vasculature inhibit additional release. Prolactin is known activate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways other cell types, including neurons. possible role JAK-STAT NEDA has therefore been examined this study...
Activation of the p38 mitogen-activated protein kinase (MAPK) pathway induces inflammation, apoptosis, and fibrosis. However, little is known contribution upstream kinases, MMK3 MKK6, to activation in kidney consequent renal injury. This study investigated MKK3 MAPK injury obstructed kidney. Groups eight wild-type (WT) or Mkk3-/- mice underwent unilateral ureteric obstruction (UUO) were killed 3 7 days later. Western blotting showed a marked increase phospho-p38 (p-p38) UUO WT The same trend...
The role of macrophages in promoting interstitial fibrosis the obstructed kidney is controversial. Macrophage depletion studies unilateral ureter obstruction (UUO) model have produced opposing results, presumably reflecting subtleties individual methods used. To address this question, we targeted macrophage colony-stimulating factor receptor, c-fms, which uniquely expressed by cells monocyte/macrophage lineage. Administration 5, 12.5, or 30 mg/kg (bid) a selective inhibitor c-fms kinase...
<i>Background/Aims:</i> The c-Jun amino-terminal kinase (JNK) signaling pathway is activated in human kidney diseases and promotes renal injury experimental glomerulonephritis. In this study, we examined whether JNK plays a role the development of diabetic nephropathy or regulating hypertension, which exacerbates injury. <i>Methods:</i> Diabetes was induced spontaneously hypertensive rats (SHR) using streptozotocin. At week 16 diabetes, with equivalent hyperglycemia...
Prolactin secretion from the anterior pituitary is tightly regulated by feedback onto hypothalamic neuroendocrine dopaminergic (NEDA) neurons. stimulates these neurons to synthesize and secrete dopamine, which acts via portal vasculature inhibit prolactin lactotrophs. Despite physiological importance of this feedback, relatively little known about signaling mechanisms responsible for activation NEDA This issue has been examined here using a cell culture preparation fetal rat mediobasal...
To determine whether matrix metalloproteinase-12 (MMP-12) plays a functional role in renal interstitial macrophage accumulation, fibrosis or tubular apoptosis the unilateral ureteric obstruction (UUO) model.MMP-12 is an enzyme that can cleave number of extracellular proteins and macrophage-mediated injury experimental models emphysema antibody-dependent glomerular disease. Macrophages are thought to promote damage obstructed kidney. Furthermore, upregulation MMP-12 expression by infiltrating...
Cyclophilin A (CypA) is a highly abundant protein in the cytoplasm of most mammalian cells. Beyond its homeostatic role folding, CypA Damage-Associated Molecular Pattern which can promote inflammation during tissue injury. However, kidney disease largely unknown. This study investigates contribution two different types injury: acute tubular necrosis and progressive interstitial fibrosis. (Ppia) gene deficient wild type (WT) littermate controls underwent bilateral renal ischaemia/reperfusion...
Senescence of kidney tubules leads to tubulointerstitial fibrosis (TIF). Proximal tubular epithelial cells undergo stress-induced senescence during diabetes and episodes acute injury (AKI), combining these injuries promotes the progression diabetic disease (DKD). Since TIF is crucial DKD, we examined therapeutic potential targeting with a senolytic drug (HSP90 inhibitor) and/or senostatic (ASK1 in model which AKI superimposed on diabetes. After 8 weeks streptozotocin-induced diabetes, mice...
Cells of the monocyte/macrophage lineage have been implicated as effectors in acute allograft rejection based on short-term depletion studies. However, therapeutic potential targeting monocyte/macrophages is unknown. We investigated a c-fms kinase inhibitor (fms-I) renal rejection.Lewis rats underwent bilateral nephrectomy and received an orthotopic Dark Agouti allograft. Recipients fms-I or vehicle from time transplantation until being killed day 5.Vehicle-treated developed severe with...