A5022601269- Cardiac Fibrosis and Remodeling
- Cell Adhesion Molecules Research
- Renin-Angiotensin System Studies
- Heart Failure Treatment and Management
- Signaling Pathways in Disease
- Connective tissue disorders research
- Protease and Inhibitor Mechanisms
- Bone Metabolism and Diseases
- Cytokine Signaling Pathways and Interactions
- Cardiovascular Effects of Exercise
- Viral Infectious Diseases and Gene Expression in Insects
- biodegradable polymer synthesis and properties
- Parathyroid Disorders and Treatments
- Cellular Mechanics and Interactions
- Cardiovascular Function and Risk Factors
- Craniofacial Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immune Response and Inflammation
- Colorectal Cancer Treatments and Studies
- Alcohol Consumption and Health Effects
- Fibroblast Growth Factor Research
- Ion Transport and Channel Regulation
- Nitric Oxide and Endothelin Effects
- Hedgehog Signaling Pathway Studies
- Cancer-related gene regulation
University of California, San Diego
2012-2023
Kyungpook National University
2010
University of California San Diego Medical Center
1999-2005
Ottawa Regional Cancer Foundation
1994-2000
University of Ottawa
1998-2000
St Vincent's Hospital
1990
ANG-(1-7) improves the function of remodeling heart. Although this peptide is generated directly within myocardium, effects on cardiac fibroblasts that play a critical role in are largely unknown. We tested hypothesis specific binding to regulates cellular functions involved remodeling. 125I-labeled assays identified sites adult rat (ARCFs) with an affinity 11.3 nM and density 131 fmol/mg protein. At nanomolar concentrations, interacted were distinct from ANG II type 1 2 receptors without...
Activating protein (AP)-1 transcription factors modulate expression of genes involved in cell proliferation and migration. Chronic hypoxia increases pulmonary artery smooth muscle by upregulating AP-1-responsive encoding for endothelium-derived vasoactive mitogenic implicated hypertension development. The AP-1 is sensitive to changes cytosolic free [Ca2+] ([Ca2+]cyt). Capacitative Ca2+ entry (CCE) via store-operated channels (SOC) an important mechanism raising [Ca2+]cyt endothelial cells...
Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-α (TNF-α) and angiotensin (Ang) II levels increase MI both factors affect fibroblast functions. The type 1 (AT ) receptor that mediates most Ang effects upregulated in fibroblasts, there evidence this caused by TNF-α. We sought to determine if TNF-α–induced AT upregulation alters responsiveness effect differs from direct TNF-α on In cultured neonatal...
Development of the craniofacial skeleton requires interactions between progenitor cells and collagen-rich extracellular matrix (ECM). The mediators these are not well-defined. Mutations in discoidin domain receptor 2 gene ( DDR2 ), which encodes a non-integrin collagen receptor, associated with human abnormalities, such as midface hypoplasia open fontanels. However, exact role this morphogenesis is known. As will be shown, Ddr2 -deficient mice exhibit defects bones including impaired...
LAMP2 is a ubiquitously expressed protein critical for autophagy. Alternative splicing gives rise to three isoforms. However, the roles of major isoforms in heart are not known. To address this knowledge gap, we generated lamp2a and lamp2b knockout (KO) mice investigate role these function Deletion either Lamp2a or Lamp2b did alter cardiac structure function. Lack all led increased fibrosis reduced survival during pressure overload, which were observed KO mice. Also, LAMP2B loss affect...
Abstract —Angiotensin II (Ang II) plays an important role in post–myocardial infarction (MI) remodeling. Most Ang effects related to remodeling involve activation of the type 1 receptor (AT ). Although AT is upregulated on cardiac fibroblasts post-MI, little known about mechanisms involved process. Consequently, we tested whether growth factors be present heart increased mRNA levels. Using quantitative competitive reverse transcription–polymerase chain reaction, found that norepinephrine,...
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta up-regulate type 1 angiotensin II receptor (AT(1)) mRNA protein in cultured neonatal rat cardiac fibroblasts. The use of pharmacologic inhibitors a degradation-resistant mutant I kappa B-alpha demonstrated that the transcription factor nuclear factor-kappa B (NF-kappa B) is necessary for cytokine-induced AT(1) up-regulation. increase with TNF-alpha treatment slow, reaching significance by 6-12 h peaking 24-48 h. Electrophoretic...
Excessive collagen deposition by myofibroblasts during adverse cardiac remodeling leads to myocardial fibrosis that can compromise function. Unraveling the mechanisms underlying gene expression in is therefore an important clinical goal. The receptors, discoidin domain receptor 2 (DDR2), a collagen-specific tyrosine kinase, and integrin-β1, are reported mediate tissue fibrosis. Here, we probed role of DDR2-integrin-β1 cross-talk regulation α1(I) angiotensin II (Ang II)-stimulated...
Abstract Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor kinase that, together with integrins, required for cells to respond the extracellular matrix. Ddr2 loss-of-function mutations in humans and mice cause severe defects skeletal growth development. However, cellular functions of bone are not understood. Expression lineage analysis showed selective expression at early stages formation resting zone proliferating chondrocytes periosteum. Consistent these findings, + could...
Discoidin domain receptor 2 (DDR2) is a fibrillar collagen that expressed in mesenchymal cells throughout the body. In heart, DDR2 selectively on cardiac fibroblasts. We generated germline knockout mouse and used this to examine role of deletion heart structure function. Echocardiographic measurements from null mice were consistent with those smaller reduced left ventricular chamber dimensions little change wall thickness. Fractional shortening appeared normal. Left pressure revealed mild...
Abstract Stimulation of human peripheral blood granulocytes with the proinflammatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), increases incorporation [3H]uridine into RNA. We investigated nature RNA synthesized under these conditions. Using transcription inhibitors, gel electrophoresis, and high-salt precipitation, it was concluded that as much 90% this radiolabeled represents polymerase II transcripts. Differential display reverse transcription-polymerase chain...
When human peripheral blood granulocytes were metabolically labeled at 37 degrees C with [32P]orthophosphate, inorganic polyphosphates became preferentially radiolabeled. Incorporation of radiolabel into the polymer appeared to be ATP-independent. [32P]Polyphosphate was identified by its (i) characteristic lability acid hydrolysis, (ii) insolubility in barium acetate (pH 4.5), (iii) conversion [32P]trimetaphosphate, (iv) hydrolysis [32P]orthophosphate an exopolyphosphate (Saccharomyces...
Angiotensin II (ANG II) plays important roles in cardiac extracellular matrix remodeling via its type 1A (AT(1A)) receptor. The cytokines tumor necrosis factor-alpha and interleukin-1beta (IL-1beta) were shown previously to upregulate AT(1A) receptor mRNA protein, thereby increasing the profibrotic response ANG fibroblasts. present experiments implicate increased nuclear factor-kappaB (NF-kappaB)-dependent transcription also, a lesser extent, altered splicing mechanism of upregulation....
This study probed the largely unexplored regulation and role of fibronectin in Angiotensin II-stimulated cardiac fibroblasts. Using gene knockdown overexpression approaches, Western blotting, promoter pull-down assay, we show that collagen type I-activated Discoidin Domain Receptor 2 (DDR2) mediates II-dependent transcriptional upregulation by Yes-activated Protein Furthermore, siRNA-mediated attenuated expression I anti-apoptotic cIAP2, enhanced fibroblast susceptibility to apoptosis....
TEGT is a conserved, widely expressed gene transcript of unknown function that has been studied previously only at the nucleic acid level. The deduced amino sequence predicts highly hydrophobic, 26.5 kDa integral membrane protein with seven potential transmembrane domains. Little else known about because lack definitive homology to other sequences and absence informative consensus motifs. present report details preliminary study human (hTEGT) protein. (i) In vitro translation hTEGT in...
Measurement of thymidylate synthase (hTS) using immunohistochemical techniques has been reported in several clinical studies. However, its value as a prognostic indicator is still not clear. To pursue this, we have developed new rabbit polyclonal antibody, hTS7.4. The antigen was recombinant hTS containing an N-terminal His 6 -tag. Antiserum hTS7.4 detected by ELISA at titer 1:100,000. Western blot analysis human cell lines showed single band the expected 36-kD molecular size. HeLa cells...