Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion
The activation of cardiac fibroblasts (CFs) after myocardial infarction (MI) is essential for post-MI infarct healing, during which the regulation of transforming growth factor beta1 (TGF-β1) signaling is predominant. We have demonstrated that TGF-β1-mediated upregulation of LBH contributes to post-...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2022/8939449 |
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| author | Yuling Xu Anbiao Wu Jingyang Chen Xudong Song Minsheng Chen Qicai Liu |
| author_facet | Yuling Xu Anbiao Wu Jingyang Chen Xudong Song Minsheng Chen Qicai Liu |
| author_sort | Yuling Xu |
| collection | DOAJ |
| description | The activation of cardiac fibroblasts (CFs) after myocardial infarction (MI) is essential for post-MI infarct healing, during which the regulation of transforming growth factor beta1 (TGF-β1) signaling is predominant. We have demonstrated that TGF-β1-mediated upregulation of LBH contributes to post-MI CF activation via modulating αB-crystallin (CRYAB), after being upregulated by TGF-β1. In this study, the effect of LBH-CRYAB signaling on the cardiac microenvironment via exosome communication and the corresponding mechanisms were investigated. The upregulation of LBH and CRYAB was verified in both cardiomyocytes (CMs) and CFs in hypoxic, post-MI peri-infarct tissues. CM-derived exosomes were isolated and identified, and LBH distribution was elevated in exosomes derived from LBH-upregulated CMs under hypoxia. Treatment with LBH+ exosomes promoted cellular proliferation, differentiation, and epithelial-mesenchymal transition-like processes in CFs. Additionally, in primary LBHKO CFs, western blotting showed that LBH knockout partially inhibited TGF-β1-induced CF activation, while LBH-CRYAB signaling affected TGF-β1 expression and secretion through a positive feedback loop. The administration of a Smad3 phosphorylation inhibitor to LBHKO CFs under TGF-β1 stimulation indicated that Smad3 phosphorylation partially accounted for TGF-β1-induced LBH upregulation. In conclusion, LBH upregulation in CMs in post-MI peri-infarct areas correlated with a hypoxic cardiac microenvironment and led to elevated exosomal LBH levels, promoting the activation of recipient CFs, which brings new insights into the studies and therapeutic strategies of post-MI cardiac repair. |
| format | Article |
| id | doaj-art-c7ad5712f4a046599dcd2f5e5aa5532a |
| institution | OA Journals |
| issn | 1466-1861 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-c7ad5712f4a046599dcd2f5e5aa5532a2025-08-20T02:19:36ZengWileyMediators of Inflammation1466-18612022-01-01202210.1155/2022/8939449Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome SecretionYuling Xu0Anbiao Wu1Jingyang Chen2Xudong Song3Minsheng Chen4Qicai Liu5Nanfang HospitalGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular DiseaseNanfang HospitalGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular DiseaseGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular DiseaseGuangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular DiseaseThe activation of cardiac fibroblasts (CFs) after myocardial infarction (MI) is essential for post-MI infarct healing, during which the regulation of transforming growth factor beta1 (TGF-β1) signaling is predominant. We have demonstrated that TGF-β1-mediated upregulation of LBH contributes to post-MI CF activation via modulating αB-crystallin (CRYAB), after being upregulated by TGF-β1. In this study, the effect of LBH-CRYAB signaling on the cardiac microenvironment via exosome communication and the corresponding mechanisms were investigated. The upregulation of LBH and CRYAB was verified in both cardiomyocytes (CMs) and CFs in hypoxic, post-MI peri-infarct tissues. CM-derived exosomes were isolated and identified, and LBH distribution was elevated in exosomes derived from LBH-upregulated CMs under hypoxia. Treatment with LBH+ exosomes promoted cellular proliferation, differentiation, and epithelial-mesenchymal transition-like processes in CFs. Additionally, in primary LBHKO CFs, western blotting showed that LBH knockout partially inhibited TGF-β1-induced CF activation, while LBH-CRYAB signaling affected TGF-β1 expression and secretion through a positive feedback loop. The administration of a Smad3 phosphorylation inhibitor to LBHKO CFs under TGF-β1 stimulation indicated that Smad3 phosphorylation partially accounted for TGF-β1-induced LBH upregulation. In conclusion, LBH upregulation in CMs in post-MI peri-infarct areas correlated with a hypoxic cardiac microenvironment and led to elevated exosomal LBH levels, promoting the activation of recipient CFs, which brings new insights into the studies and therapeutic strategies of post-MI cardiac repair.http://dx.doi.org/10.1155/2022/8939449 |
| spellingShingle | Yuling Xu Anbiao Wu Jingyang Chen Xudong Song Minsheng Chen Qicai Liu Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion Mediators of Inflammation |
| title | Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion |
| title_full | Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion |
| title_fullStr | Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion |
| title_full_unstemmed | Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion |
| title_short | Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion |
| title_sort | limb bud and heart lbh upregulation in cardiomyocytes under hypoxia promotes the activation of cardiac fibroblasts via exosome secretion |
| url | http://dx.doi.org/10.1155/2022/8939449 |
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