American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2015
Rare Variants in RTEL1 are Associated with Familial Interstitial Pneumonia.
Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. ⋯ Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.
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Am. J. Respir. Crit. Care Med. · Mar 2015
Loss of miR-17~92 in Smooth Muscle Cells Attenuates Experimental Pulmonary Hypertension via Induction of PDLIM5.
Recent studies suggest that microRNAs (miRNAs) play important roles in regulation of pulmonary artery smooth muscle cell (PASMC) phenotype and are implicated in pulmonary arterial hypertension (PAH). However, the underlying molecular mechanisms remain elusive. ⋯ We provided the first evidence that miR-17∼92 inhibits PDLIM5 to induce the TGF-β3/SMAD3 pathway, contributing to the pathogenesis of PAH.
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Am. J. Respir. Crit. Care Med. · Mar 2015
Comparative StudyAmpakines Enhance Weak Endogenous Respiratory Drive and Alleviate Apnea in Perinatal Rats.
Apnea of prematurity, which is prevalent among infants born at less than 34 weeks gestation, is treated with caffeine, theophylline, or aminophylline. However, not all newborns respond adequately to, or tolerate, methylxanthine administration, and thus alternative pharmacological therapies are required. ⋯ The net effect of ampakine enhancement of respiratory drive in perinatal rodents is a marked increase in ventilation and the regularity of respiratory patterns in perinatal rat preparations. Importantly, from the perspective of clinical applications, CX1739 readily crosses the blood-brain barrier, is metabolically stable, and has passed through phase I and II clinical trials in adults.
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Am. J. Respir. Crit. Care Med. · Mar 2015
Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation.
Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. ⋯ Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans.
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Am. J. Respir. Crit. Care Med. · Mar 2015
Impaired BMPRII Signalling in a TGFβ Dependent Mouse Model of Pulmonary Hypertension and in Systemic Sclerosis.
Up to 10% of patients with systemic sclerosis (SSc) develop pulmonary arterial hypertension (PAH). This risk persists throughout the disease and is time dependent, suggesting that SSc is a susceptibility factor. Outcome for SSc-PAH is poor compared with heritable or idiopathic forms, despite clinical and pathological similarities. Although susceptibility in heritable PAH and idiopathic PAH is strongly associated with gene mutations leading to reduced expression of bone morphogenetic protein receptor (BMPR) II, these mutations have not been observed in SSc-PAH. ⋯ We found reduced BMPRII protein in patients with SSc-PAH and a relevant mouse model associated with increased proteasomal degradation of BMPRII. Collectively, these results suggest that impaired BMP signaling, resulting from TGF-β-dependent increased receptor degradation, may promote PAH susceptibility in SSc and provide a unifying mechanism across different forms of PAH.