This SuperSeries is composed of the SubSeries listed below.
NF-κB activation impairs somatic cell reprogramming in ageing.
Specimen part, Disease, Disease stage, Treatment
View SamplesTo study how changes in the nuclear mechanical properties may modify the development of Ventilator-induced lung injury, mice of both genotypes were studied at baseline or after 2.5 hours of mechanical ventilation (PIP 15cmH2O, ZEEP, 100 breaths/min, inspiratory:expiratory ratio 1:1, inpired oxygen fraction 0.21).After that, mice were sacrificed, the lungs estracted and gene expression measured in order to identify the differential gene expression depending on the different nuclear stifness.
No associated publication
Sex, Age, Specimen part
View SamplesDietary intervention constitutes a feasible approach for modulating metabolism and improving healthspan and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and alters the levels of bile acids, both in wild-type and in progeroid mice. Notably, treatment with the bile acid cholic acid improves healthspan and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.
Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism.
Sex, Age, Specimen part
View SamplesPancreatic islet transplantation was performed in the subcutaneous space of diabetic nude mice. In order to promote long survival and function of transplanted islets a plasma-based scaffold was developed in combination with fibroblasts as graft-supporting accesory cells. Gene expression analysis was carried out to evaluate expression differences due to the presence of fibroblast which could explain the long-term glycemic control observed under these circumstances.
Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.
Disease, Time
View SamplesThe identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase paralleling the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b-/- mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. Atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohns disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b-/- mice. Taken together, these results provide additional evidence on the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that Atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency
ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.
Sex, Age, Specimen part, Treatment
View SamplesTo study the effects of previous exposure to mechanical ventilation may modify the development of Ventilator-induced lung injury, preconditioning was induced by low-pressure ventilation for 90 minutes. After 1 week, intact (sham) and preconditioned mice were sacrificed, the lungs extracted and gene expression measured in order to identify differences responsible for the observed tolerance to ventilator-induced lung injury observed in preconditioned animals.
Exposure to mechanical ventilation promotes tolerance to ventilator-induced lung injury by Ccl3 downregulation.
Age, Specimen part
View SamplesTranscriptional profiling of human control and Nstor-Guillermo Progeria Syndrome (NGPS) mesenchymal stem cells (MSCs).
NF-κB activation impairs somatic cell reprogramming in ageing.
Specimen part, Disease, Disease stage, Treatment
View SamplesTranscriptional profiling of human acute myeloid leukemia cells lines HEL and SET2 transduced with an IGF1R shRNA and miR-125a sponge.
Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling.
Specimen part, Cell line, Treatment
View SamplesHutchinson-Gilford Progeria Syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. We report herein a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. By using this animal model, we have developed an antisense morpholinobased therapy that prevents the pathogenic Lmna splicing, dramatically reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotidebased therapies for treating human diseases of accelerated aging.
Splicing-directed therapy in a new mouse model of human accelerated aging.
Sex, Age, Specimen part
View SamplesAdamts12-deficient mice undergo more severe colitis than WT mice after induction with DSS.
ADAMTS-12 metalloprotease is necessary for normal inflammatory response.
Specimen part, Treatment
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