The Effects of the Anti-aging Protein Klotho on Mucociliary Clearance.

α-klotho (KL) is an anti-aging protein and has been shown to exert anti-inflammatory and anti-oxidative effects in the lung and pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. The current study investigated the direct effect of KL on the bronchial epithelium in regards to mucociliary clearance parameters. Primary human bronchial and murine tracheal epithelial cells, cultured, and differentiated at the air liquid interface (ALI), were treated with recombinant KL or infected with a lentiviral vector expressing KL.

Losartan Rescues Inflammation-related Mucociliary Dysfunction in Relevant Models of Cystic Fibrosis.

Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large-conductance Ca-activated and voltage-dependent K (BK) channels, critical for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator). To test losartan as an antiinflammatory therapy in CF using CF human bronchial epithelial cells and an ovine model of CF-like airway disease.

Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia.

Chronic inflammation is a hallmark of cystic fibrosis (CF) and associated with increased production of transforming growth factor (TGF) β and interleukin (IL)-8. α-klotho (KL), a transmembrane or soluble protein, functions as a co-receptor for Fibroblast Growth Factor (FGF) 23, a known pro-inflammatory, prognostic marker in chronic kidney disease. KL is downregulated in airways from COPD patients.

Modulation of Wnt signaling is essential for the differentiation of ciliated epithelial cells in human airways.

Wnt signaling is essential for the differentiation of airway epithelial cells during development. Here, we examined the role of Wnt signaling during redifferentiation of ciliated airway epithelial cells in vitro at the air liquid interface as a model of airway epithelial repair. Phases of proliferation and differentiation were defined.

Role of Smad3 and p38 Signalling in Cigarette Smoke-induced CFTR and BK dysfunction in Primary Human Bronchial Airway Epithelial Cells.

Mucociliary clearance (MCC) is a major airway host defence system that is impaired in patients with smoking-associated chronic bronchitis. This dysfunction is partially related to a decrease of airway surface liquid (ASL) volume that is in part regulated by apically expressed cystic fibrosis transmembrane conductance regulator (CFTR) and large-conductance, Ca-activated, and voltage dependent K (BK) channels. Here, data from human bronchial epithelial cells (HBEC) confirm that cigarette smoke not only downregulates CFTR activity but also inhibits BK channel function, thereby causing ASL depletion.

Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration.

Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration.

Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss.

ERRs and cancers: effects on metabolism and on proliferation and migration capacities.

ERRs are orphan members of the nuclear receptor superfamily which, at least for ERRα and ERRγ display important roles in the control of various metabolic processes. On other hand, correlations have been found between the expression of ERRα and γ and diverse parameters of tumor progression in human cancers. Whereas it is tempting to speculate that ERR receptors act in tumors through the regulation of metabolism, recent data have suggested that they also may directly regulate tumor proliferation and progression independently of their effects on metabolism.