RESUMEN
After injury, the coordinated balance of pro- and anti-inflammatory factors in the microenvironment contribute to skeletal muscle regeneration. However, the underlying molecular mechanisms regulating this balance remain incompletely understood. In this study, we examined the roles of microRNAs (miRNAs) in inflammation and muscle regeneration. miRNA-Seq transcriptome analysis of mouse skeletal muscle revealed that miR-223-3p is upregulated in the early stage of muscle regeneration after injury. miR-223-3p knockout resulted in increased inflammation, impaired muscle regeneration, and increased interstitial fibrosis. Mechanistically, we found that myeloid-derived miR-223-3p suppresses the target gene interleukin-6 (Il6), associated with the maintenance of the proinflammatory macrophage phenotype during injury. Administration of IL-6-neutralizing antibody in miR-223-3p-knockout muscle could rescue the impaired regeneration ability and reduce the fibrosis. Together, our results reveal that miR-223-3p improves muscle regeneration by regulating inflammation, indicating that miRNAs can participate in skeletal muscle regeneration by controlling the balance of pro- and anti-inflammatory factors in the skeletal muscle microenvironment.
Asunto(s)
MicroARNs/biosíntesis , Músculo Esquelético , Regeneración , Regulación hacia Arriba , Animales , Inflamación/genética , Inflamación/metabolismo , Interleucina-6/biosíntesis , Interleucina-6/genética , Ratones , Ratones Noqueados , MicroARNs/genética , Músculo Esquelético/lesiones , Músculo Esquelético/fisiología , RNA-SeqRESUMEN
This study aims to explore the effects of arachidonic acid lipoxygenase metabolism in vascular calcification. We used 5/6 nephrectomy and high-phosphorus feeding to establish a model of vascular calcification in mice. Six weeks after nephrectomy surgery, vascular calcium content was measured, and Alizarin Red S and Von Kossa staining were applied to detect calcium deposition in aortic arch. Control aortas and calcified aortas were collected for mass spectrometry detection of arachidonic acid metabolites, and active molecules in lipoxygenase pathway were analyzed. Real-time quantitative PCR was used to detect changes in the expression of lipoxygenase in calcified aortas. Lipoxygenase inhibitor was used to clarify the effect of lipoxygenase metabolic pathways on vascular calcification. The results showed that 6 weeks after nephrectomy surgery, the aortic calcium content of the surgery group was significantly higher than that of the sham group (P < 0.05). Alizarin Red S staining and Von Kossa staining showed obvious calcium deposition in aortic arch from surgery group, indicating formation of vascular calcification. Nine arachidonic acid lipoxygenase metabolites were quantitated using liquid chromatography/mass spectrometry (LC-MS) analysis. The content of multiple metabolites (12-HETE, 11-HETE, 15-HETE, etc.) was significantly increased in calcified aortas, and the most abundant and up-regulated metabolite was 12-HETE. Furthermore, we examined the mRNA levels of metabolic enzymes that produce 12-HETE in calcified blood vessels and found the expression of arachidonate lipoxygenase-15 (Alox15) was increased. Blocking Alox15/12-HETE by Alox15 specific inhibitor PD146176 significantly decreased the plasma 12-HETE content, promoted calcium deposition in aortic arch and increased vascular calcium content. These results suggest that the metabolism of arachidonic acid lipoxygenase is activated in calcified aorta, and the Alox15/12-HETE signaling pathway may play a protective role in vascular calcification.
Asunto(s)
Ácidos Hidroxieicosatetraenoicos , Calcificación Vascular , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico , Animales , Araquidonato 12-Lipooxigenasa , Araquidonato 15-Lipooxigenasa/metabolismo , Ácido Araquidónico , Lipooxigenasa/metabolismo , Ratones , Transducción de SeñalRESUMEN
The objective of this study was to explore the roles of arachidonic acid cytochrome P450ω hydroxylase CYP4A14 in skeletal muscle regeneration after injury. Wild-type (WT) control mice and Cyp4a14 knockout (A14-/-) mice were used to establish the muscle injury and regeneration model by intramuscular injection with cardiotoxin (CTX) on the tibial anterior (TA) muscle. The TA muscles were harvested at the time points of 0, 3, 5 and 15 days after injury. The changes in skeletal muscle regeneration and fibrosis were assessed by wheat germ agglutinin (WGA) staining and Sirius Red staining. Immunohistochemical staining was used to observe the expression of proliferation-related protein Ki-67 and macrophage marker protein Mac-2. The mRNA levels of regeneration and inflammation associated genes were analyzed by real-time PCR. The results showed that the cross-section area (CSA) of regenerated myofibers in A14-/- mice was significantly smaller (P < 0.05), while the percentage of fibrosis area was significantly higher than those in WT mice at 15 days after injury (P < 0.05). In A14-/- muscles, both the ratio of Ki-67 positive proliferating cells and the mRNA levels of differentiation associated genes Myod1 and Myog were significantly lower than those in WT muscles (P < 0.05). At 3 days after injury, the mRNA expression of inflammatory cells marker genes CD45 and CD11b and Mac-2 positive macrophages in A14-/- muscles were significantly lower than those in WT skeletal muscle (P < 0.05). Macrophages derived pro-regeneration cytokines IL-1ß, IGF-1 and SDF-1 were also significantly decreased in A14-/- muscles (P < 0.05). These results suggest that arachidonic acid cytochrome P450ω hydroxylase CYP4A14 plays a critical role in skeletal muscle regeneration after injury.
Asunto(s)
Oxigenasas de Función Mixta , Regeneración , Animales , Ácido Araquidónico , Citocromos , Técnicas de Inactivación de Genes , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo EsqueléticoRESUMEN
Cotton is one of the most important crops in the world. With the increasing scarce of global water resources, irrigation water will become a major limiting factor in cotton production. Deficit irrigation is an irrigation method which consumes less water than the normal evapotranspiration of crops. It is an effective water-saving method due to improved water use efficiency without sacrificing cotton yield and fiber quality. We summarized the effects of deficit irrigation on the growth and water use efficiency of cotton. The results showed that deficit irrigation promoted the transformation from vegetative growth to reproductive growth, reduced plant height, leaf area, and total biomass of cotton, and subsequently improved the harvest index, stem diameter and water use efficiency. Finally, based on the current research and combined with cotton production reality, the application and future development of deficit irrigation were proposed, which might provide theoretical guidance for the sustainable development of cotton plantation in arid areas.
Asunto(s)
Riego Agrícola , Agua , Biomasa , Productos Agrícolas , Hojas de la PlantaRESUMEN
The unique anti-atherosclerosis abilities and other cardioprotective properties make high-density lipoprotein (HDL) a promising solution in treating cardiovascular diseases. A number of studies showed that HDL-based therapy was well tolerated and has great potential in the future. Among all these new agents, the most studied ones including recombinant HDL, recombinant human apolipoproteins, apolipoprotein mimetic peptides and recombinant HDL used as contrast agents in cardiovascular imaging are discussed here. Recombinant HDL and apolipoproteins are promising in diagnosing and treating cardiovascular diseases.