Annual review of physiology
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Despite public health campaigns discouraging smoking, 1,000 American children every day become smokers, ensuring that tobacco-related health complications will be with us for decades to come. Smoking is the greatest risk factor for both chronic obstructive lung disease and interstitial lung disease. ⋯ In this review, we explore common and divergent biological forces tilting the lung homeostatic balance away from health and toward emphysema or pulmonary fibrosis. We emphasize recent insights that highlight the greatest contrasts or similarities in the pathogenesis of these two chronic lung disease phenotypes.
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Annu. Rev. Physiol. · Jan 2013
ReviewFibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism.
The metabolically active and perpetually remodeling calcium phosphate-based endoskeleton in terrestrial vertebrates sets the demands on whole-organism calcium and phosphate homeostasis that involves multiple organs in terms of mineral flux and endocrine cross talk. The fibroblast growth factor (FGF)-Klotho endocrine networks epitomize the complexity of systems biology, and specifically, the FGF23-αKlotho axis highlights the concept of the skeleton holding the master switch of homeostasis rather than a passive target organ as hitherto conceived. ⋯ This review covers recent data on the physiological regulation and function of the complex FGF23-αKlotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-αKlotho, a multiorgan endocrine network, is deranged in a self-amplifying vortex resulting in organ dysfunction of the utmost severity that contributes to its morbidity and mortality.
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Annu. Rev. Physiol. · Jan 2013
ReviewRegulation and repair of the alveolar-capillary barrier in acute lung injury.
Considerable progress has been made in understanding the basic mechanisms that regulate fluid and protein exchange across the endothelial and epithelial barriers of the lung under both normal and pathological conditions. Clinically relevant lung injury occurs most commonly from severe viral and bacterial infections, aspiration syndromes, and severe shock. ⋯ Repair mechanisms include the participation of endogenous progenitor cells in strategically located niches in the lung. Novel treatment strategies include the possibility of cell-based therapy that may reduce the severity of lung injury and enhance lung repair.
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(Macro)autophagy provides a membrane-dependent mechanism for the sequestration, transport, and lysosomal turnover of subcellular components, including proteins and organelles. In this capacity, autophagy maintains basal cellular homeostasis and healthy organelle populations such as mitochondria. During starvation, autophagy prolongs cell survival by recycling metabolic precursors from intracellular macromolecules. ⋯ Increasing evidence suggests that autophagy, and its regulatory proteins, may critically influence vital cellular processes such as programmed cell death, cell proliferation, inflammation, and innate immune functions and thereby may play a critical role in the pathogenesis of human disease. The function of autophagy in disease pathogenesis remains unclear and may involve either impaired or accelerated autophagic activity or imbalances in the activation of autophagic proteins. This review examines the roles of autophagy in the pathogenesis of pulmonary diseases, with emphasis on pulmonary vascular disease and acute and chronic lung diseases.
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Annu. Rev. Physiol. · Jan 2010
Biography Historical ArticleA conversation with Rita Levi-Montalcini.