Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes

Author:

Boronat-Toscano Albert1ORCID,Vañó Irene1,Monfort-Ferré Diandra1,Menacho Margarita2,Valldosera Gemma2,Caro Aleidis3ORCID,Espina Beatriz3,Mañas Maria José4,Marti Marc5,Espin Eloy5ORCID,Saera-Vila Alfonso6,Serena Carolina1ORCID

Affiliation:

1. Hospital Universitari de Tarragona Joan XXIII, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43007 Tarragona, Spain

2. Digestive Unit, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain

3. Colorectal Surgery Unit, Hospital Universitari Joan XXIII, 43007 Tarragona, Spain

4. Colorectal Surgery Unit, Hospital San Pau i Santa Tecla, 43003 Tarragona, Spain

5. Colorectal Surgery Unit, General Surgery Service, Hospital Vall de Hebron, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain

6. Sequentia Biotech, Carrer Comte D’Urgell 240, 08036 Barcelona, Spain

Abstract

Patients with Crohn’s disease (CD) who smoke are known to have a worse prognosis than never-smokers and a higher risk for post-surgical recurrence, whereas patients who quit smoking after surgery have significantly lower post-operative recurrence. The hypothesis was that smoking induces epigenetic changes that impair the capacity of adipose stem cells (ASCs) to suppress the immune system. It was also questioned whether this impairment remains in ex-smokers with CD. ASCs were isolated from non-smokers, smokers and ex-smokers with CD and their interactions with immune cells were studied. The ASCs from both smokers and ex-smokers promoted macrophage polarization to an M1 pro-inflammatory phenotype, were not able to inhibit T- and B-cell proliferation in vitro and enhanced the gene and protein expression of inflammatory markers including interleukin-1b. Genome-wide epigenetic analysis using two different bioinformatic approaches revealed significant changes in the methylation patterns of genes that are critical for wound healing, immune and metabolic response and p53-mediated DNA damage response in ASCs from smokers and ex-smokers with CD. In conclusion, cigarette smoking induces a pro-inflammatory epigenetic signature in ASCs that likely compromises their therapeutic potential.

Funder

Spanish Ministry of Economy and Competitiveness

European Regional Development Fund

Ministerio de Educación y Ciencia

PI-AGAUR

INVESTIGO-AGAUR

PERIS-PFI-Salut

Publisher

MDPI AG

Subject

General Medicine

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3