A5055144202- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Medical Imaging and Pathology Studies
- Liver Disease Diagnosis and Treatment
- Ion Transport and Channel Regulation
- Renal Diseases and Glomerulopathies
- Congenital Diaphragmatic Hernia Studies
- Parathyroid Disorders and Treatments
- Chronic Kidney Disease and Diabetes
- Lung Cancer Treatments and Mutations
- Pulmonary Hypertension Research and Treatments
- Diet, Metabolism, and Disease
- Drug Transport and Resistance Mechanisms
- Birth, Development, and Health
- Adipose Tissue and Metabolism
- Magnesium in Health and Disease
- Inhalation and Respiratory Drug Delivery
- Biomedical Research and Pathophysiology
- Hepatitis C virus research
- Galectins and Cancer Biology
- Drug-Induced Hepatotoxicity and Protection
- Tracheal and airway disorders
- Liver Disease and Transplantation
- Peptidase Inhibition and Analysis
- Helicobacter pylori-related gastroenterology studies
University of Colorado Anschutz Medical Campus
2016-2025
University of Colorado Denver
2016-2025
University of Colorado System
2024
Pediatrics and Genetics
2022
University of Tsukuba
2018
University of Colorado Health
2014
Given the phenotypic similarities between rheumatoid arthritis (RA)–associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that strongest risk factor for development of gain-of-function MUC5B promoter variant rs35705950, would also contribute to ILD among patients with RA.
Intestinal epithelial cells (IECs) are exposed to profound fluctuations in oxygen tension and have evolved adaptive transcriptional responses a low-oxygen environment. These adaptations mediated primarily through the hypoxia-inducible factor (HIF) complex. Given central role of IEC barrier function, we sought determine whether HIF influenced tight junction (TJ) structure function. Initial studies revealed that short hairpin RNA-mediated depletion HIF1β T84 resulted defects nonuniform,...
The gain-of-function MUC5B promoter variant rs35705950 is the dominant risk factor for developing idiopathic pulmonary fibrosis (IPF). Here we show in humans that MUC5B, a mucin thought to be restricted conducting airways, co-expressed with surfactant protein C (SFTPC) type 2 alveolar epithelia and epithelial cells lining honeycomb cysts, indicating cell types involved lung distal airspace express MUC5B. In mice, demonstrate Muc5b concentration bronchoalveolar related impaired mucociliary...
Bile acids are ligands for the nuclear hormone receptor farnesoid X (FXR) and G protein-coupled TGR5. We have shown that FXR TGR5 renoprotective roles in diabetes- obesity-related kidney disease. Here, we determined whether these effects mediated through differential or synergistic signaling pathways. administered FXR/TGR5 dual agonist INT-767 to DBA/2J mice with streptozotocin-induced diabetes, db/db type 2 C57BL/6J high-fat diet-induced obesity. also examined individual of selective...
Approximately 200 million people throughout the world are infected with hepatitis C virus (HCV). One of most striking features HCV infection is its high propensity to establish persistence (∼70–80%) and progressive liver injury. Galectins evolutionarily conserved glycan-binding proteins diverse roles in innate adaptive immune responses. Here, we demonstrate that galectin-9, natural ligand for T cell immunoglobulin domain mucin protein 3 (Tim-3), circulates at very levels serum hepatic...
Obesity and diabetes mellitus are the leading causes of renal disease. In this study, we determined regulation role G protein-coupled bile acid receptor TGR5, previously shown to be regulated by high glucose and/or fatty acids, in obesity-related glomerulopathy (ORG) diabetic nephropathy (DN). Treatment db/db mice with selective TGR5 agonist INT-777 decreased proteinuria, podocyte injury, mesangial expansion, fibrosis, CD68 macrophage infiltration kidney. also induced expression master...
Significance Intestinal epithelial barrier dysregulation is a hallmark of inflammatory bowel diseases (IBDs). A central role for hypoxic signaling has been defined in modulation during inflammation. We demonstrate that genes involved creatine metabolism, the kinases (CKs), are coordinately regulated by hypoxia-inducible transcription factors (HIFs) and such regulation critical to function. Inhibition CK pathway abrogates apical junction assembly integrity. Dietary supplementation profoundly...
Background: Diastolic dysfunction (DD) is associated with the development of heart failure and contributes to pathogenesis other cardiac maladies, including atrial fibrillation. Inhibition histone deacetylases (HDACs) has been shown prevent DD by enhancing myofibril relaxation. We addressed therapeutic potential HDAC inhibition in a model established preserved ejection fraction. Methods: Four weeks after uninephrectomy implantation deoxycorticosterone acetate pellets, when was clearly...
Abstract The airway epithelium serves as the interface between host and external environment. In many chronic lung diseases, is site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease alveolus matrix, dominant environmental (cigarette smoking) genetic (gain function MUC5B promoter variant) risk factor primarily affect distal epithelium. Moreover, airway-specific pathogenic features IPF include bronchiolization...
Cytokines secreted at sites of inflammation impact the onset, progression, and resolution inflammation. In this article, we investigated potential proresolving mechanisms IFN-γ in models inflammatory bowel disease. Guided by initial microarray analysis, vitro studies revealed that selectively induced expression IL-10R1 on intestinal epithelia. Further analysis was expressed predominantly apical membrane polarized epithelial cells. Receptor activation functionally canonical IL-10 target gene...
Soluble klotho, the shed ectodomain of antiaging membrane protein α-klotho, is a pleiotropic endocrine/paracrine factor with no known receptors and poorly understood mechanism action. klotho down-regulates growth factor-driven PI3K signaling, contributing to extension lifespan, cardioprotection, tumor inhibition. Here we show that soluble binds lipid rafts. Klotho binding rafts alters organization, decreases membrane's propensity form large ordered domains for endocytosis, raft-dependent...
The renal glomerulus forms a selective filtration barrier that allows the passage of water, ions, and small solutes into urinary space while restricting cells macromolecules. three layers glomerular include vascular endothelium, basement membrane (GBM), podocyte epithelium. Podocytes are capable internalizing albumin hypothesized to clear proteins traverse GBM. present study followed fate FITC-labeled establish mechanisms endocytosis processing by podocytes. Confocal imaging total internal...
Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to increasing prevalence of these diseases, yet mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, functional levels bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile...
Pulmonary hypertension (PH) is a heterogeneous and life-threatening cardiopulmonary disorder in which mitochondrial dysfunction believed to drive pathogenesis, although the underlying mechanisms remain unclear. To determine if abnormal SIRT3 (sirtuin 3) activity related adventitial fibroblasts from patients with idiopathic pulmonary arterial (IPAH) hypoxic PH calves (PH-Fibs) whether could be potential therapeutic target improve function, concentrations control fibroblasts, PH-Fibs, lung...
The ability of the adult heart to regenerate cardiomyocytes (CMs) lost after injury is limited, generating interest in developing efficient cell-based transplantation therapies. Rigid carbon nanotubes (CNTs) scaffolds have been used improve CMs viability, proliferation, and maturation, but they require undesirable invasive surgeries for implantation. To overcome this limitation, we developed an injectable reverse thermal gel (RTG) functionalized with CNTs (RTG-CNT) that transitions from a...
Increasingly, evidence suggests that exposure to maternal obesity creates an inflammatory environment in utero , exerting long‐lasting postnatal signatures on the juvenile innate immune system and microbiome may predispose offspring development of fatty liver disease. We found a Western‐style diet (WD) accelerated fibrogenesis was associated with early recruitment proinflammatory macrophages at 8‐12 weeks microbial dysbiosis as 3 age. further demonstrated bone marrow‐derived (BMDMs) were...
Idiopathic pulmonary fibrosis (IPF) is a genetically mediated, age-associated, progressive form of characterised pathologically by usual interstitial pneumonia (UIP) pattern fibrosis. The UIP also found in attributable to clinical diagnoses other than IPF (non-IPF UIP), whose course similarly poor, suggesting common molecular drivers. This study investigates whether and non-IPF lungs express markers telomere dysfunction senescence.To test patients with share drivers, lung tissues from 169 57...
Rationale: Common genetic variants have been associated with idiopathic pulmonary fibrosis (IPF). Objectives: To determine functional relevance of the 10 IPF-associated common we previously identified. Methods: We performed expression quantitative trait loci (eQTL) and methylation (mQTL) mapping, followed by co-localization eQTL mQTL association signals validation luciferase reporter assays. Illumina multi-ethnic genotyping arrays, mRNA sequencing, 850k arrays were on lung tissue...