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Macrophage migration inhibitory factor confers resistance to senescence through CD74-dependent AMPK-FOXO3a signaling in mesenchymal stem cells

Overview of attention for article published in Stem Cell Research & Therapy, April 2015
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Title
Macrophage migration inhibitory factor confers resistance to senescence through CD74-dependent AMPK-FOXO3a signaling in mesenchymal stem cells
Published in
Stem Cell Research & Therapy, April 2015
DOI 10.1186/s13287-015-0076-3
Pubmed ID
Authors

Wenzheng Xia, Fengyun Zhang, Congying Xie, Miaomiao Jiang, Meng Hou

Abstract

Mesenchymal stem cells (MSCs)- based therapies have had positive outcomes in animal models of cardiovascular diseases. However, the number and function of MSCs decline with age, reducing their ability to contribute to endogenous injury repair. The potential of stem cells to restore damaged tissue in older individuals can be improved by specific pretreatment aimed at delaying senescence and improving their regenerative properties. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that modulates age- related signaling pathways, and hence is a good candidate for rejuvenative function. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were isolated from young (6-month-old) or aged (24-month-old) male donor rats. Cell proliferation was measured using the CCK8 cell proliferation assay; secretion of VEGF, bFGF, HGF, and IGF was assessed by RT-qPCR and ELISA. Apoptosis was induced by hypoxia and serum deprivation (hypoxia/SD) for up to 6 hr, and examined by flow cytometry. Expression levels of AMP-activated protein kinase (AMPK) and forkhead box class O 3a (FOXO3a) were detected by Western blotting. CD74 expression was assayed using RT-qPCR, Western blotting, and immunofluorescence. In this study, we found that MSCs isolated from the bone marrow of aged rats displayed reduced proliferative capacity, impaired ability to mediate paracrine signaling, and lower resistance to hypoxia/serum deprivation- induced apoptosis, when compared to younger MSCs. Interestingly, pretreatment of aged MSCs with MIF enhanced their growth, paracrine function and survival. We detected enhanced secretion of VEGF, bFGF, HGF, and IGF from MIF- treated MSCs using ELISA. Finally, we show that hypoxia/serum deprivation- induced apoptosis is inhibited in aged MSCs following MIF exposure. Next, we found that the mechanism underlying the rejuvenating function of MIF involves increased CD74- dependent phosphorylation of AMPK and FOXO3a. Furthermore, this effect was abolished when CD74, AMPK, or FOXO3a expression was silenced using small-interfering RNAs(siRNA). MIF can rejuvenate MSCs from a state of age-induced senescence by interacting with CD74 and subsequently activating AMPK-FOXO3a signaling pathways. Pretreatment of MSCs with MIF may have important therapeutic implications in restoration or rejuvenation of endogenous bone marrow-MSCs in aged individuals.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Sweden 1 2%
Unknown 41 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 19%
Researcher 7 17%
Student > Master 5 12%
Student > Bachelor 4 10%
Student > Doctoral Student 3 7%
Other 6 14%
Unknown 9 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 19%
Medicine and Dentistry 7 17%
Agricultural and Biological Sciences 4 10%
Immunology and Microbiology 4 10%
Neuroscience 4 10%
Other 4 10%
Unknown 11 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 September 2015.
All research outputs
#14,808,845
of 22,800,560 outputs
Outputs from Stem Cell Research & Therapy
#1,204
of 2,418 outputs
Outputs of similar age
#148,784
of 265,536 outputs
Outputs of similar age from Stem Cell Research & Therapy
#40
of 76 outputs
Altmetric has tracked 22,800,560 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,418 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 265,536 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 76 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.