Evidence map›Paper›PMID 24760207›Full record

ArticleStem cells translational medicine2014

Crosstalk between adrenergic and toll-like receptors in human mesenchymal stem cells and keratinocytes: a recipe for impaired wound healing.

Mohan R Dasu, Sandra R Ramirez, Thi Dinh La, Farzam Gorouhi, Chuong Nguyen, Benjamin R Lin, Chelcy Mashburn, Heather Stewart, Thomas R Peavy, Jan A Nolta and 1 more

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.6field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
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  8. Review
  9. [Mechanisms of adrenergic β-antagonist for wounds and its application prospect in diabetic foot ulcers].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2020
    Review
  10. Article
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  16. Stem Cells in Spinal Fusion.Global spine journal · 2017
    Article
  17. Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Mohan R DasuDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA rrisseroff@ucdavis.edu rkdasu@ucdavis.edu rkmdasu@gmail.com.
Sandra R RamirezDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Thi Dinh LaDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Farzam GorouhiDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Chuong NguyenDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Benjamin R LinDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Chelcy MashburnDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Heather StewartDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Thomas R PeavyDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Jan A NoltaDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
Roslyn R IsseroffDepartment of Dermatology and Institute for Regenerative Cures, University of California, Davis, California, USA; Department of Biological Sciences, California State University, Sacramento, California, USA; Dermatology Service, Department of Veterans Affairs, Northern California Health Care System, Sacramento, California, USA rrisseroff@ucdavis.edu rkdasu@ucdavis.edu rkmdasu@gmail.com.
University of California, Davis · USCalifornia State University, Sacramento · USCalifornia Institute for Regenerative Medicine · US

Funding

Direct cell to cell transfer of microRNA for tissue repairR01GM099688 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI NOLTA, JAN A. · 2011 to 2015
$2.7M
Predoctoral Training in Pharmacological SciencesT32GM099608 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HELL, JOHANNES W · 2012 to 2021
$2.2M
Molecular mechanisms and novel therapeutic approaches to combined radiation and bR33AI080604 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ISSEROFF, ROSLYN RIVKAH, ROCKE, DAVID M. · 2011 to 2013
$1.2M
Molecular mechanisms and novel therapeutic approaches to combined radiation and bR21AI080604 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ISSEROFF, ROSLYN RIVKAH, ROCKE, DAVID M. · 2008 to 2009
$426k
NIAID NIH HHS R21 AI080604NIAID NIH HHS R33 AI080604NIAID NIH HHS R34 AI080604NIGMS NIH HHS 1R01GM099688NIGMS NIH HHS R01 GM099688NIGMS NIH HHS T32 GM099608
6 · The paper itself

Abstract

Previous studies demonstrate that skin wounds generate epinephrine (EPI) that can activate local adrenergic receptors (ARs), impairing healing. Bacterially derived activators of Toll-like receptors (TLRs) within the wound initiate inflammatory responses and can also impair healing. In this study, we examined the hypothesis that these two pathways crosstalk to one another, using EPI and macrophage-activating lipopeptide-2 (MALP2) to activate ARs and TLR2, respectively, in human bone marrow-derived mesenchymal stem cells (BM-MSCs) and neonatal keratinocytes (NHKs). BM-MSCs exposed to EPI significantly (p < .05) increased TLR2 message (sevenfold BM-MSCs), TLR2 protein (twofold), and myeloid differentiation factor 88 (MyD88) (fourfold). Conversely, activation of TLR2 by MALP2 in these cells increased β2-AR message (twofold in BM-MSCs, 2.7-fold in NHKs), β2-AR protein (2.5-fold), phosphorylation of β-AR-activated kinase (p-BARK, twofold), and induced release of EPI from both cell types (twofold). Treating cells with EPI and MALP2 together, as would be encountered in a wound, increased β2-AR and p-BARK protein expression (sixfold), impaired cell migration (BM-MSCs- 21%↓ and NHKs- 60%↓, p < .002), and resulted in a 10-fold (BM-MSCs) and 51-fold (NHKs) increase in release of IL-6 (p < .001) responses that were remarkably reduced by pretreatment with β2-AR antagonists. In vivo, EPI-stressed animals exhibited impaired healing, with elevated levels of TLR2, MyD88, and IL-6 in the wounds (p < .05) relative to nonstressed controls. Thus, our data describe a recipe for decreasing cell migration and exacerbating inflammation via novel crosstalk between the adrenergic and Toll-like receptor pathways in BM-MSCs and NHKs.

Indexed as

Cell CommunicationReceptor Cross-TalkStem Cell TransplantationWound HealingAdrenergic beta-AgonistsAdrenergic beta-AntagonistsAnimalsCell MovementCells, CulturedEpinephrineG-Protein-Coupled Receptor Kinase 2HumansInterleukin-6KeratinocytesLipopeptidesMaleADRB2 protein, humanAdrenergic beta-AgonistsAdrenergic beta-AntagonistsEpinephrineG-Protein-Coupled Receptor Kinase 2GRK2 protein, humanIL6 protein, humanInterleukin-6interleukin-6, mouseLipopeptidesmacrophage stimulatory lipopeptide 2MYD88 protein, humanMyeloid Differentiation Factor 88Receptors, Adrenergic, beta-2TLR2 protein, humanTlr2 protein, mouseToll-Like Receptor 2Cell migrationCell signalingMesenchymal stem cellsStem cell-microenvironment interactionsTissue regeneration

Identifiers

PMID24760207
PMCPMC4039457
OpenAlexW2133764165

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.