eprintid: 205615 rev_number: 35 eprint_status: archive userid: 9223 dir: disk0/00/20/56/15 datestamp: 2019-12-12 16:08:13 lastmod: 2024-10-29 13:29:59 status_changed: 2019-12-12 16:08:13 type: article metadata_visibility: show creators_name: McArthur, Lisa creators_name: Riddell, Alexandra creators_name: Chilton, Lisa creators_name: Smith, Godfrey L. creators_name: Nicklin, Stuart A. creators_orcid: 0000-0002-8014-640X creators_orcid: 0000-0003-4566-8680 creators_orcid: 0000-0003-4821-9741 creators_orcid: 0000-0002-9691-6210 title: Regulation of connexin 43 by interleukin 1β in adult rat cardiac fibroblasts and effects in an adult rat cardiac myocyte: fibroblast co-culture model ispublished: pub divisions: 25200000 full_text_status: public abstract: Connexin 43 expression (Cx43) is increased in cardiac fibroblasts (CFs) following myocardial infarction. Here, potential mediators responsible for increasing Cx43 expression and effects of differential CF phenotype on cardiac myocyte (CM) function were investigated. Stimulating adult rat CFs with proinflammatory mediators revealed that interleukin 1β (IL-1β) significantly enhanced Cx43 levels through the IL-1β pathway. Additionally, IL-1β reduced mRNA levels of the myofibroblast (MF) markers: (i) connective tissue growth factor (CTGF) and (ii) α smooth muscle actin (αSMA), compared to control CFs. A co-culture adult rat CM:CF model was utilised to examine cell-to-cell interactions. Transfer of calcein from CMs to underlying CFs suggested functional gap junction formation. Functional analysis revealed contraction duration (CD) of CMs was shortened in co-culture with CFs, while treatment of CFs with IL-1β reduced this mechanical effect of co-culture. No effect on action potential rise time or duration of CMs cultured with control or IL-1β-treated CFs was observed. These data demonstrate that stimulating CFs with IL-1β increases Cx43 and reduces MF marker expression, suggesting altered cell phenotype. These changes may underlie the reduced mechanical effects of IL-1β treated CFs on CD of co-cultured CMs and therefore have an implication for our understanding of heterocellular interactions in cardiac disease. date: 2020-01 date_type: published publication: Heliyon volume: 6 number: 1 publisher: Elsevier id_number: 10.1016/j.heliyon.2019.e03031 refereed: TRUE issn: 2405-8440 copyright_holders: Copyright © 2019 The Author(s) prior: First published in Heliyon 6(1): e03031 repro: Reproduced under a Creative Commons license uniqueid: glaseprints:2020-205615 issn_online: 2405-8440 funding_project_code: 167019 funding_project_name: BHF 4 Year PhD Programme funding_investigator_name: Anna Dominiczak funding_funder_name: British Heart Foundation (BHF) funding_funder_code: FS/12/66/30003 funding_investigator_dept: Institute of Cardiovascular & Medical Sciences article_number: e03031 pubmed_id: 31909243 euro_pubmed_id: 31909243 pmcid: PMC6940628 hoa_compliant: 9023 hoa_ref_pan: AB hoa_date_acc: 2019-12-10 hoa_date_pub: 2019-12-30 hoa_date_foa: 2020-02-28 hoa_version_fcd: AM hoa_exclude: FALSE hoa_gold: TRUE oa_research_materials_ack: Yes oa_invoice_cost: 1180 oa_invoice_cost: 236 oa_invoice_number: OAD0000023650 oa_invoice_number: OAD0000023650/1 citation: McArthur, L. , Riddell, A. , Chilton, L. , Smith, G. L. and Nicklin, S. A. (2020) Regulation of connexin 43 by interleukin 1β in adult rat cardiac fibroblasts and effects in an adult rat cardiac myocyte: fibroblast co-culture model. Heliyon , 6(1), e03031. (doi: 10.1016/j.heliyon.2019.e03031 ) (PMID:31909243) (PMCID:PMC6940628) document_url: https://eprints.gla.ac.uk/205615/12/205615.pdf