We have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis.
Exposure to cadmium (Cd) has been associated with development of chronic obstructive lung disease (COPD). The mechanisms and signaling pathways whereby Cd causes pathological peribronchiolar fibrosis, airway remodeling and subsequent airflow obstruction remain unclear. We aimed to evaluate whether low dose Cd exposure induces vimentin phosphorylation and YAP1 activation leading to peribronchiolar fibrosis and subsequent airway remodeling.
Given the diabesity and Metabolic Syndrome epidemics, fatty liver disease is reaching epidemic proportions. Relatively indolent, this disease is often asymptomatic and the patient is often made aware of its presence only during a routine physical exam. Nevertheless, fatty livers are more susceptible to insult compared to their non-fatty counterparts and persons with fatty livers are at increased risk for morbidity and mortality following consumption of commonly used substances such as alcohol (EtOH) and acetaminophen (APAP).
Hepatic stellate cells (HSCs) activate during injury to orchestrate the liver's inflammatory and fibrogenic responses. A critical feature of HSC activation is the rapid induction of β-PDGFR, which drives cellular fibrogenesis and proliferation; in contrast, normal liver has minimal β-PDGFR expression.