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LL-37 stimulates the functions of adipose-derived stromal/stem cells via early growth response 1 and the MAPK pathway

Overview of attention for article published in Stem Cell Research & Therapy, April 2016
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Title
LL-37 stimulates the functions of adipose-derived stromal/stem cells via early growth response 1 and the MAPK pathway
Published in
Stem Cell Research & Therapy, April 2016
DOI 10.1186/s13287-016-0313-4
Pubmed ID
Authors

Yoolhee Yang, Hyunju Choi, Mira Seon, Daeho Cho, Sa Ik Bang

Abstract

LL-37 is a naturally occurring antimicrobial peptide found in the wound bed and assists wound repair. No published study has characterized the role of LL-37 in the function(s) of human mesenchymal stem cells (MSCs). This study investigated the functions of adipose-derived stromal/stem cells (ASCs) activated by LL-37 by performing both in vitro assays with cultured cells and in vivo assays with C57BL/6 mice with hair loss. Human ASCs were isolated from healthy donors with written informed consent. To examine the effects of LL-37 on ASC function, cell proliferation and migration were measured by a cell counting kit (CCK-8) and a Transwell migration assay. Early growth response 1 (EGR1) mRNA expression was determined by microarray and real-time PCR analyses. The protein levels of EGR1 and regenerative factors were analyzed by specific enzyme-linked immunosorbent assays and western blotting. LL-37 treatment enhanced the proliferation and migration of human ASCs expressing formyl peptide receptor like-1. Microarray and real-time PCR data showed that EGR1 expression was rapidly and significantly increased by LL-37 treatment. LL-37 treatment also enhanced the production of EGR1. Moreover, small interfering RNA-mediated knockdown of EGR1 inhibited LL-37-enhanced ASC proliferation and migration. Activation of mitogen-activated protein kinases (MAPKs) was essential not only for LL-37-enhanced ASC proliferation and migration but also EGR1 expression; treatment with a specific inhibitor of extracellular signal-regulated kinase, p38, or c-Jun N-terminal kinase blocked the stimulatory effect of LL-37. EGR1 has a strong paracrine capability and can influence angiogenic factors in ASCs; therefore, we evaluated the secretion levels of vascular endothelial growth factor, thymosin beta-4, monocyte chemoattractant protein-1, and stromal cell-derived factor-1. LL-37 treatment increased the secretion of these regenerative factors. Moreover, treatment with the conditioned medium of ASCs pre-activated with LL-37 strongly promoted hair growth in vivo. These findings show that LL-37 increases EGR1 expression and MAPK activation, and that preconditioning of ASCs with LL-37 has a strong potential to promote hair growth in vivo. This study correlates LL-37 with MSC functions (specifically those of ASCs), including cell expansion, cell migration, and paracrine actions, which may be useful in terms of implantation for tissue regeneration.

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Mendeley readers

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The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Singapore 1 2%
Unknown 49 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 10%
Student > Bachelor 5 10%
Professor > Associate Professor 5 10%
Student > Master 5 10%
Student > Postgraduate 3 6%
Other 5 10%
Unknown 23 45%
Readers by discipline Count As %
Medicine and Dentistry 8 16%
Biochemistry, Genetics and Molecular Biology 5 10%
Nursing and Health Professions 2 4%
Agricultural and Biological Sciences 2 4%
Immunology and Microbiology 2 4%
Other 6 12%
Unknown 26 51%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 02 January 2017.
All research outputs
#15,369,653
of 22,865,319 outputs
Outputs from Stem Cell Research & Therapy
#1,343
of 2,422 outputs
Outputs of similar age
#179,629
of 299,207 outputs
Outputs of similar age from Stem Cell Research & Therapy
#23
of 34 outputs
Altmetric has tracked 22,865,319 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,422 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 34th percentile – i.e., 34% 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 299,207 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.