Project description:Previously we have shown that AML12 cell-derived extracellular vesicles (EVs) exhibit anti-fibrotic effects in human hepatic stellate cells in vitro and during toxin-induced liver injury in mice. The mechanisms by which AML12 EVs ameliorate liver fibrosis have not been fully investigated and microRNAs are among the EV payload components that are delivered to recepient cells to regulate their functionsl properties. In this study, EVs were isolated by differential centrifugation of culture supernatants from AML12 cells that ahd been maintained in serum-free conditions. The EVs were characterized by Nanosight Tracking Analysis and Western blot. Three different batches of AML12 EVs were used to isolate total RNAs by QIAGEN miRNeasy kit, and approximately 200 ng of RNAs were subjected to small RNA-seq. A total of 224 miRNAs were identified, with miR-122-5p, miR-378a-3p, miR-210-3p, miR-320-3p, and miR-125a-5p ranked as the top five most abundant miRNAs.
Project description:DUSP6 plays important roles in MAPK signaling pathway, but whether and how it is involved in liver funciton remains to be explored. Here, we performed RNA-seq analyses in AML12 cells where DUSP6 is disrupted. We overexpressed GFP-DUSP6 or GFP in AML12 cells, and tested the effects of DUSP6 increase on gene expression in AML12 cells. Meanwhile, we knocked down DUSP6 in AML12 cells and tested the effects of DUSP6 decrease on gene expression in AML12 cells. Taken together, we analyzed the changes of gene expression mediated by DUSP6, which provides new insights for the function of DUSP6 in liver
Project description:In our study, we aimed to provide a comprehensive cytogenetic and genomic profiling of the murine AML12 hepatocyte cell line. We established an integrated reference map that combines cytogenetics, short tandem repeat (STR) profiling, and transcriptomic analysis through RNA sequencing. Our findings reveal that AML12 maintains hepatocyte lineage identity while exhibiting partial de-differentiation and a complex karyotypic landscape characterized by a near-tetraploid chromosome set with recurrent structural rearrangements. This study serves as a valuable resource for the scientific community, enhancing the understanding of AML12's genetic characteristics and its implications for future research in liver biology and related fields.
Project description:Physical activity is thought to provide clinical benefit in Parkinson’s diseas (PD). Irisin is a blood-brain barrier permeable exercise-induced polypeptide secreted by muscle that mediates, in part, the beneficial effects of exercise. Here we show that irisin prevents pathologic -synuclein (-syn) induced neurodegeneration in the -syn preformed fibril mouse model of sporadic PD. Intravenous delivery of adenoviral irisin in vivo after the stereotaxic intrastriatal injection of -syn pre-formed fibrils reduced the formation of pathologic -syn and prevented the loss of dopamine neurons and reductions in striatal dopamine. Irisin also reduced the -syn pre-formed fibril induced motor deficits as assessed by the pole test and grip strength test. Administration of recombinant irisin in primary cortical neurons prevented pathologic -syn toxicity. Tandem mass spectrometry and biochemical analysis revealed that irisin reduced pathologic -syn by enhancing endolysosomal degradation of pathologic -syn. Our findings highlight the potential for therapeutic disease modification of irisin in PD.
Project description:Irisin is a recently identified myokine that is induced by exercise and stimulates brown-fat-like development of white fat and energy expenditure in humans and mice. In this study, we aimed to evaluate the pro-proliferative effect of irisin on C2C12 myoblasts and its mechanisms of action.
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
Project description:Irisin is secreted by muscle, increased with exercise, and conveys certain physiological benefits. Earlier studies showed that short-term irisin treatment caused browning of subcutaneous white fat in mice, with improved glucose tolerance; the effects of more chronic irisin treatment and mechanisms at play have not been explored. We demonstrate here that chronic irisin application improves obesity and dramatically reduces glucose intolerance. This treatment increases an IL-33+ mesenchymal stromal cell (mSC) population, while genetic ablation of irisin reduces plasma IL-33 levels and decreases thermogenic gene expression in subcutaneous adipose tissue. Importantly, irisin directly induces IL-33 expression in mSCs and stimulates ST2+regulatory T (Treg) cells, inducing their tissue accumulation. Inhibition of IL-33 blunts these irisin-mediated effects on energy expenditure and glucose homeostasis, largely through IL33-mediated regulation of ST2+ Treg cells. These data indicate that irisin improves obesity and glucose intolerance, with no muscle loss, through a key immunomodulatory pathway in obese mice .