Search results for "Fibrosis"

Role of MUC1 in idiopathic pulmonary fibrosis: mechanistic insights

2017

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible form of fibrotic interstitial lung disease. MUC1, a membrane-bound O-glycoprotein, is considered as oncogenic molecule by altering signaling pathways involved in cellular processes related to IPF. In previous studies we have observed an up-regulation of MUC1 and its phosphorylated forms in IPF lung tissue. However the exact participation of MUC1 in IPF is currently unknown. Objective: To analyze the mechanism of MUC1-induced lung fibrosis in different cellular and animal models of IPF. Methods: The intracellular mechanism of MUC1 was evaluated by western blot, immunoprecipation and immunofluorescence …

Liquid biomarkers for fibrotic NASH – progress in a complex field

2022

<i>NR1H4</i> rs35724 G>C Variant Modulates Liver Damage in Nonalcoholic Fatty Liver Disease

2020

Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 variant, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms was genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n=124). Results: The NR1H4 rs35724 variant was protective against severity of steatosis (OR 0.89, 95% C.I.…

Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

2020

AbstractObesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms remain incompletely understood. Here we demonstrate that macrophage scavenger receptor 1 (MSR1, CD204) expression is associated with the occurrence of hepatic lipid-laden foamy macrophages and correlates with the degree of steatosis and steatohepatitis in a cohort of 170 NAFLD patients. Mice lacking Msr1 are protected against high fat-cholesterol diet (HFD)-induced metabolic disorder, showing fewer hepatic lipid-laden foamy macrophages, less hepatic inflammation, improved dyslipidemia and glucose tolerance, while showing a change in hepatic …

Differential PI3K signal transduction in obesity-associated cardiac hypertrophy and response to ischemia

2014

Objective Elevated insulin and inflammatory cytokine levels in obesity may chronically activate signaling pathways regulating cardiac growth and contractility. Our aim was to examine the effect of obesity on cardiac PI3K isoform and Akt activation during left ventricular (LV) hypertrophy and heart failure. Methods Wild-type mice were fed normal chow or high-fat diet (HFD) for 2, 4, or 6 months. A subset of mice was subjected to chronic myocardial ischemia (MI). Results Echocardiography revealed a progressive increase in LV mass, wall thickness, and diameters in obese mice. Systolic pump function was not impaired. Increased cardiac levels of PI3Kγ, phosphorylated Akt, GSK3β, and Epac were ob…

Muc1 bioactivation contributes to lung fibrosis

2019

INTRODUCCIÓN La fibrosis pulmonar idiopática (FPI) es una forma específica de neumonía intersticial fibrosante, progresiva, crónica y de causa desconocida. Recientemente se ha propuesto que la FPI surge a partir de episodios repetidos de daño en las células epiteliales alveolares, lo cual puede estar asociado con una liberación de mediadores profibróticos (como el factor de crecimiento transformante β1 (TGFβ1)), fomentando la activación descontrolada de fibroblastos, transformaciones celulares en células mesenquimales de tipo miofibroblasto y una acumulación excesiva de matriz extracelular en el intersticio pulmonar, lo cual destruye la arquitectura alveolar normal e interrumpe el intercamb…

Estudio farmacológico ex vivo/in vitro de vasos pulmonares humanos de pacientes con fibrosis pulmonar e hipertensión pulmonar

2018

Sildenafilo mejora el test 6 minutos marcha en pacientes con fibrosis pulmonar idiopática (FPI) y disfunción sistólica ventricular derecha. Teniendo esto en cuenta, analizamos el papel previamente inexplorado de sildenafilo en la vasoconstricción y la remodelación de las arterias pulmonares de pacientes con FPI e hipertensión pulmonar (HP) ex vivo/in vitro. Se obtuvieron anillos arteriales pulmonares procedentes de: 18 pulmones sin enfermedad pulmonar, nueve con FPI, ocho con FPI + HP y cuatro con HP. Se midieron los efectos vasodilatadores y anticontráctiles de sildenafilo en un baño de órganos isométrico, se estudió su repercusión en el remodelado vascular en muestras ex vivo e in vitro y…

Combinación de realce tardío de gadolinio en cardiorresonancia y actividad adrenérgica con 123I-MIBG en la estratificación pronóstica en pacientes co…

2019

INTRODUCCIÓN: la insuficiencia cardíaca (IC) tiene elevadas prevalencia e incidencia, así como morbilidad y mortalidad. Actualmente, la IC se ha convertido en un problema de salud pública y la mayoría de las muertes son debidas a causas cardiovasculares, principalmente muerte súbita cardíaca (MSC). La fracción de eyección (FEVI) es un importante predictor de eventos cardiovasculares en pacientes con disfunción sistólica de ventrículo izquierdo (VI). Los datos europeos más recientes (estudio ESC-HF long term) demuestran que las tasas de mortalidad por causa cardíaca son mayores en pacientes con IC con FEVI reducida que con FEVI conservada. Y en pacientes con IC la mayoría de las muertes son …

International BEAT-PCD Consensus Statement for Infection Prevention and Control for Primary Ciliary Dyskinesia in collaboration with ERN-LUNG PCD Cor…

2021

Introduction In primary ciliary dyskinesia (PCD) impaired mucociliary clearance leads to recurrent airway infections and progressive lung destruction, and concern over chronic airway infection and patient-to-patient transmission is considerable. So far, there has been no defined consensus on how to control infection across centres caring for patients with PCD. Within the BEAT-PCD network, COST Action and ERS CRC together with the ERN-Lung PCD core a first initiative has now been taken towards creating such a consensus statement. Methods A multidisciplinary international PCD expert panel was set up to create a consensus statement for infection prevention and control (IP&C) for PCD, covering …

The combination of PDE4 and PDE5 inhibitors reduces YAP expression in IPF

2017

Background: Pathological fibrosis is associated with repeated episodes of injury to alveolar epithelial cells of largely. Yes-associated protein (YAP) is prominently expressed in fibrotic lung. Roflumilast has demonstrated to exhibit anti-fibrosis effects, while PDE5 inhibitors (sildenafil) combinated with PDE4 inhibitors reduce fibrotic-effects secondary to TGFs1. Apparently, no studies of PDE4 and PDE5 inhibitors on YAP expression there are. Objectives: To study the effects from adding a sildenafil to Roflumilast N- oxide (RNO) on TGF-β/SMAD3/YAP pathway in IPF in vitro models. Methods: A549 cells were pre-incubated with therapeutical concentrations of RNO (2nM) and/or sildenafil (10nM) a…