American journal of physiology. Cell physiology
-
Am. J. Physiol., Cell Physiol. · Dec 2019
Burn-induced reductions in mitochondrial abundance and efficiency are more pronounced with small volumes of colloids in swine.
Severe burn injury results in systemic disruption of metabolic regulations and impaired cardiac function. Restoration of hemodynamic homeostasis utilizing intravenous (IV) fluids is critical for acute care of the burn victim. However, the effects of burns and resuscitation on cardiomyocyte mitochondria are currently unknown. ⋯ Taken together, severe burns alter mitochondrial respiration in heart tissue, which may be exacerbated by early IV resuscitation with colloids. Early IV burn resuscitation with colloids may require close hemodynamic observation. Mitochondrial stabilizing agents incorporated into resuscitation fluids may help the hemodynamic response to burn injury.
-
Am. J. Physiol., Cell Physiol. · Nov 2019
Long non-coding RNA HOXA11-AS induces type I collagen synthesis to stimulate keloid formation via sponging miR-124-3p and activation of Smad5 signaling.
Keloid, characterized by exuberant collagen deposition and invasive growth beyond original wound margins, results from abnormal wound healing. A recent microarray analysis identified homeobox (HOX) A11 antisense (HOXA11-AS) as a keloid-specific long non-coding RNA, although its potential role in keloid formation remains elusive. In this study, hematoxylin-eosin, Masson, and immunohistochemical staining of type I collagen (ColI) revealed abnormal arrangement and hyperplasia of fibers in keloid tissues along with increased ColI level. qRT-PCR and Western blot showed that HOXA11-AS and ColI were significantly upregulated, while miR-124-3p was decreased in both keloid tissues and human keloid fibroblasts (HKFs). ⋯ Mechanistic experiments verified that HOXA11-AS acted as a sponge of micro-RNA (miR)-124-3p and Smad5 was a target of miR-124-3p. miR-124-3p sufficiently reversed the regulatory effects of HOXA11-AS, and Smad5 was involved in miR-124-3p-mediated biological functions. Furthermore, HOXA11-AS induced ColI synthesis via sponging miR-124-3p-mediated Smad5 signaling, thus promoting keloid formation. Overall, our study implied that HOXA11-AS induces ColI synthesis to promoted keloid formation via sponging miR-124-3p-mediated Smad5 signaling, which might offer a novel target for developing the therapy of keloid formation.
-
Am. J. Physiol., Cell Physiol. · Aug 2019
ReviewDiaphragm contractile weakness due to reduced mechanical loading: role of titin.
The diaphragm, the main muscle of inspiration, is constantly subjected to mechanical loading. Only during controlled mechanical ventilation, as occurs during thoracic surgery and in the intensive care unit, is mechanical loading of the diaphragm arrested. Animal studies indicate that the diaphragm is highly sensitive to unloading, causing rapid muscle fiber atrophy and contractile weakness; unloading-induced diaphragm atrophy and contractile weakness have been suggested to contribute to the difficulties in weaning patients from ventilator support. ⋯ Titin is a giant protein that acts as a mechanosensor regulating muscle protein expression in a sarcomere strain-dependent fashion. Thus titin is an attractive candidate for sensing the sudden mechanical arrest of the diaphragm when patients are mechanically ventilated, leading to changes in muscle protein expression. Here, we provide a novel perspective on how titin and its biomechanical sensing and signaling might be involved in the development of mechanical unloading-induced diaphragm weakness.
-
Am. J. Physiol., Cell Physiol. · Dec 2018
Downregulation of microRNA-149 in retinal ganglion cells suppresses apoptosis through activation of the PI3K/Akt signaling pathway in mice with glaucoma.
Glaucoma represents a major cause of blindness, generally associated with elevated intraocular pressure (EIOP). The aim of the present study was to investigate whether microRNA-149 (miR-149) affects retinal ganglion cells (RGCs) and the underlying mechanism based on a mouse model of chronic glaucoma with EIOP. The successfully modeled mice were administered with mimics or inhibitors of miR-149. ⋯ Additionally, downregulated miR-149 was noted to increase the levels of BTC, PI3K, and Akt in both the retinal tissues and RGCs, whereas the silencing of miR-149 was observed to promote the viability of RGC and inhibit RGC apoptosis. Taken together, the results of the current study provided validation suggesting that the downregulation of miR-149 confers protection to RGCs by means of activating the PI3K/Akt signaling pathway via upregulation of BTC in mice with glaucoma. Evidence presented indicated the promise of miR-149 inhibition as a potential therapeutic strategy for glaucoma treatment.
-
Am. J. Physiol., Cell Physiol. · Apr 2018
Acute downregulation of miR-199a attenuates sepsis-induced acute lung injury by targeting SIRT1.
MicroRNA-199a (miR-199a) is a novel gene regulator with an important role in inflammation and lung injury. However, its role in the pathogenesis of sepsis-induced acute respiratory distress syndrome (ARDS) is currently unknown. Our study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of action. ⋯ We further identified sirtuin 1 (SIRT1) as a direct target of miR-199a in alveolar macrophages, and the expression of SIRT1 was negatively correlated with the level of miR-199a. The protective role of miR-199a downregulation in LPS-stimulated alveolar macrophages and sepsis-induced ARDS could be attenuated by SIRT1 inhibitor. Taken together, these results indicate that downregulation of miR-199a might protect lung tissue against sepsis-induced ARDS by upregulation of SIRT1 through the suppression of excessive inflammatory responses and the inhibition of cellular apoptosis in lung tissue, suggesting its potential therapeutic effects on sepsis-induced ARDS.