A5065604377- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Liver Disease Diagnosis and Treatment
- Nerve injury and regeneration
- Liver physiology and pathology
- Cytokine Signaling Pathways and Interactions
- Axon Guidance and Neuronal Signaling
- Pleural and Pulmonary Diseases
- Endoplasmic Reticulum Stress and Disease
- Cardiac, Anesthesia and Surgical Outcomes
- Occupational and environmental lung diseases
- Neurogenesis and neuroplasticity mechanisms
- Connective tissue disorders research
- IL-33, ST2, and ILC Pathways
- Pharmacological Effects of Natural Compounds
- Medical Imaging and Pathology Studies
- Enhanced Recovery After Surgery
- Cardiomyopathy and Myosin Studies
- Liver Diseases and Immunity
- Congenital Diaphragmatic Hernia Studies
- Pancreatitis Pathology and Treatment
- Abdominal Surgery and Complications
- Galectins and Cancer Biology
- Drug-Induced Hepatotoxicity and Protection
- COVID-19 and healthcare impacts
Canterbury Christ Church University
2025
University of Oxford
2025
National University of Singapore
2001-2024
National Heart Centre Singapore
2016-2024
Gilead Sciences (United States)
2024
National University Heart Centre Singapore
2023
Ang Mo Kio Thye Hua Kwan Hospital
2017
University of Southern California
2006-2011
Ontario Institute for Cancer Research
2010
Montreal Clinical Research Institute
2006
Interleukin-11 is important for lung fibroblast activation in idiopathic pulmonary fibrosis, and its signaling represents a therapeutic target.
We studied the role of interleukin 11 (IL11) signaling in pathogenesis nonalcoholic steatohepatitis (NASH) using hepatic stellate cells (HSCs), hepatocytes, and mouse models NASH.We stimulated human fibroblasts, HSCs, or hepatocytes with IL11 other cytokines analyzed them by imaging, immunoblot, functional assays enzyme-linked immunosorbent assays. Mice were given injections IL11. disruption receptor subunit alpha1 gene (Il11ra1-/-) mice Il11ra1+/+ fed a high-fat methionine-...
Abstract IL11 is important for fibrosis in non-alcoholic steatohepatitis (NASH) but its role beyond the stroma liver disease unclear. Here, we investigate of hepatocyte lipotoxicity. Hepatocytes highly express IL11RA and secrete response to lipid loading. Autocrine activity causes death through NOX4-derived ROS, activation ERK, JNK caspase-3, impaired mitochondrial function reduced fatty acid oxidation. Paracrine stimulates hepatic stellate cells fibrosis. In mouse models NASH,...
Inhibition of IL11 signaling limits drug-induced liver damage and promotes hepatic regeneration in a mouse model.
Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric division and axon dendrite specification. Similarly, myelination by Schwann cells polarized, but the mechanisms involved remain unclear. Here, we show that protein Par-3 localizes asymmetrically at axon-glial junction disruption of localization, overexpression knockdown, inhibits myelination. Additionally, directly associates recruits p75 neurotrophin receptor junction, forming a complex...
Repetitive pulmonary injury causes fibrosis and inflammation that underlies chronic lung diseases such as idiopathic (IPF). Interleukin 11 (IL11) is important for fibroblast activation but the contribution of fibroblast-specific IL11 activity to fibro-inflammation not known. To address this gap in knowledge, we generated mice with loxP-flanked Il11ra1 deleted receptor adult fibroblasts (CKO mice). In bleomycin (BLM) model fibrosis, CKO had reduced lesser ERK activation, diminished immune...
Interleukin 11 (IL11) is a profibrotic cytokine, secreted by myofibroblasts and damaged epithelial cells. Smooth muscle cells (SMCs) also secrete IL11 under pathological conditions express the receptor. Here we examined effects of SMC-specific, conditional expression murine in transgenic mouse (Il11SMC). Within days transgene activation, Il11SMC mice developed loose stools progressive bleeding rectal prolapse, which was associated with 65% mortality two weeks. The bowel inflamed, fibrotic...
Transforming growth factor beta-1 (TGFβ1) is a major driver of vascular smooth muscle cell (VSMC) phenotypic switching, an important pathobiology in arterial disease. We performed RNA-sequencing TGFβ1-stimulated human aortic or VSMCs which revealed large and consistent upregulation Interleukin 11 (IL11). IL11 has unknown function VSMCs, highly express the receptor alpha, suggestive autocrine loop. In vitro, activated ERK signaling, but inhibited STAT3 activity, caused VSMC switching to...
Interleukin 11 (IL11) is highly upregulated in skin and lung fibroblasts from patients with systemic sclerosis (SSc). Here we tested whether IL11 mechanistically linked activation of human dermal (HDFs) SSc or controls.We measured serum levels volunteers early diffuse manipulated signalling HDFs using gain- loss-of-function approaches that combined molecular cellular phenotyping.In SSc, are elevated as compared healthy controls. All transforming growth factor beta (TGFβ) isoforms induced...
Background: Marfan syndrome (MFS) is associated with TGF (transforming growth factor) β–stimulated ERK (extracellular signal-regulated kinase) activity in vascular smooth muscle cells (VSMCs), which adopt a mixed synthetic/contractile phenotype. In VSMCs, TGFβ induces IL (interleukin) 11) that stimulates ERK-dependent secretion of collagens and MMPs (matrix metalloproteinases). Here, we examined the role IL11 MFS aorta. Methods: We used echocardiography, histology, immunostaining,...
The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits Schwann cell (SC) migration and promotes myelination via the p75 receptor (NTR). Despite these recent findings, expression, localization, mechanism of BDNF action has yet to be determined. Here we demonstrate that sensory neurons dorsal root ganglion (DRG) are a major source during postnatal development. expression is initially elevated before decreases dramatically after onset myelination. controlled in part by...
Myelination is dependent on complex reciprocal interactions between the Schwann cell (SC) and axon. Recent evidence suggests that SC–axon interface represents a membrane specialization essential for myelination; however, manner in which this polarized-apical domain generated remains mystery. The adhesion molecule N-cadherin enriched at colocalizes with polarity protein Par-3. asymmetric localization induced SC–SC contact. Knockdown of SCs cocultured DRG neurons disrupts Par-3 delays...
Abstract Loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and incompletely penetrant craniosynostosis. The impact LOF has not been characterized. We generated knockout ( Il11 −/− ) mice that are born expected ratios have normal hematological profiles. Lung fibroblasts from resistant to pro-fibrotic stimulation with TGFβ1. Following bleomycin-induced lung injury, protected pulmonary fibrosis exhibit lesser ERK, STAT3 NF-kB activation,...
Previously, progesterone was found to regulate the initiation and biosynthetic rate of myelin synthesis in Schwann cell/neuronal cocultures. The mRNA for cytochrome P450scc (converts cholesterol pregnenolone), 3β-hydroxysteroid dehydrogenase (3β-HSD, converts pregnenolone progesterone), receptor were be markedly induced during active synthesis. However, cells cocultures responsible these changes not identified. In this study, situ hybridization used determine localization enzymes steroid...
Formation of domains by the membrane binding motifs caveolin and src were studied in large unilamellar vesicles using fluorescence digital imaging microscopy. Caveolin, a major structural protein caveolae, contains scaffolding region (residues 82−101) that contributes to plasma membrane. A peptide (82−101) corresponding this induced formation enriched acidic lipids phosphatidylserine phosphatidylinositol-4,5-bisphosphate. Cholesterol, another predominant component was also these domains....
Titin-truncating variants (TTNtv) are the most common genetic cause of dilated cardiomyopathy. TTNtv occur in ~1% general population and causes subclinical cardiac remodeling asymptomatic carriers. In rat models with either proximal or distal TTNtv, we previously showed altered metabolism at baseline impaired function response to stress. However, molecular mechanism(s) underlying these effects remains unknown. current study, used investigate effect on autophagy mitochondrial function, which...
Interleukin-11 (IL11) is important for fibrosis and inflammation, but its role in the pancreas unclear. In pancreatitis, fibrosis, inflammation organ dysfunction are associated with pancreatic stellate cell (PSC)-to-myofibroblast transformation. Here, we show that IL11 stimulation of PSCs, which specifically express IL11RA pancreas, results transient STAT3 phosphorylation, sustained ERK activation PSC activation. contrast, IL6 PSCs caused phosphorylation did not result or Pancreatitis...
Background: Marfan Syndrome (MFS) is an inherited connective tissue disorder caused by mutations in the FBN1 (fibrillin-1) gene. Lung abnormalities are common MFS, but their pathogenesis poorly understood. IL11 (interleukin-11) causes aortic disease a mouse model of MFS and was studied here lung. Methods: We examined histological molecular phenotypes lungs Fbn1 C1041G/+ mice (mouse [mMFS]), established MFS. To identify IL11-expressing cells, we used immunohistochemistry on 4- 16-week-old :...