Restoration of primary cilia in obese adipose-derived mesenchymal stem cells by inhibiting Aurora A or extracellular signal-regulated kinase

  • Background: Obesity impairs a variety of cell types including adipose-derived mesenchymal stem cells (ASCs). ASCs are indispensable for tissue homeostasis/repair, immunomodulation, and cell renewal. It has been demonstrated that obese ASCs are defective in differentiation, motility, immunomodulation, and replication. We have recently reported that some of these defects are linked to impaired primary cilia, which are unable to properly convey and coordinate a variety of signaling pathways. We hypothesized that the rescue of the primary cilium in obese ASCs would restore their functional properties. Methods: Obese ASCs derived from subcutaneous and visceral adipose tissues were treated with a specific inhibitor against Aurora A or with an inhibitor against extracellular signal-regulated kinase 1/2 (Erk1/2). Multiple molecular and cellular assays were performed to analyze the altered functionalities and their involved pathways. Results: The treatment with low doses of these inhibitors extended the length of the primary cilium, restored the invasion and migration potential, and improved the differentiation capacity of obese ASCs. Associated with enhanced differentiation ability, the cells displayed an increased expression of self-renewal/stemness-related genes like SOX2, OCT4, and NANOG, mediated by reduced active glycogen synthase kinase 3 β (GSK3β). Conclusion: This work describes a novel phenomenon whereby the primary cilium of obese ASCs is rescuable by the low-dose inhibition of Aurora A or Erk1/2, restoring functional ASCs with increased stemness. These cells might be able to improve tissue homeostasis in obese patients and thereby ameliorate obesity-associated diseases. Additionally, these functionally restored obese ASCs could be useful for novel autologous mesenchymal stem cell-based therapies.
Metadaten
Author:Andreas Ritter, Nina-Naomi KreisORCiDGND, Alexandra Friemel, Lukas JenneweinORCiDGND, Christine Eichbaum, Christine Solbach, Frank LouwenGND, Juping Yuan
URN:urn:nbn:de:hebis:30:3-507607
DOI:https://doi.org/10.1186/s13287-019-1373-z
ISSN:1757-6512
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31412932
Parent Title (English):Stem cell research & therapy
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/08/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/08/22
Tag:Adipose-derived mesenchymal stem cells; Aurora A; Aurora Ax; Extracellular signal-regulated kinase 1/2; Glycogen synthase kinase 3 beta; Obesity; Primary cilium
Volume:10
Issue:1, Art. 255
Page Number:16
First Page:1
Last Page:16
Note:
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
HeBIS-PPN:453936970
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0