Cyclosporine A induces cardiac remodeling through TGF-β/Smad3/miR-29 signaling pathway and alters gene expression of miR-30b-5p/CaMKIIδ isoforms pathways: alleviating effects of moderate exercise
Background Cyclosporine A (CsA)-induced cardiac interstitial fibrosis and cardiac hypertrophy are highly known phenomena; however, the basic mechanisms of CsA cardiotoxicity are unclear. The present study evaluated the role of the Transforming growth factor-beta (TGF-β)/Smad3/miR-29b signaling pathw...
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| Veröffentlicht in: | Molecular biology reports 2023-07, Vol.50 (7), p.5859-5870 |
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| description | Background
Cyclosporine A (CsA)-induced cardiac interstitial fibrosis and cardiac hypertrophy are highly known phenomena; however, the basic mechanisms of CsA cardiotoxicity are unclear. The present study evaluated the role of the Transforming growth factor-beta (TGF-β)/Smad3/miR-29b signaling pathway and CaMKIIδ isoforms gene expression in cardiac remodeling under CsA exposure alone or combined with moderate exercise.
Methods
A total of 24 male Wistar rats were divided into control, cyclosporine (30 mg/kg BW), and cyclosporine-exercise groups.
Results
After 42 days of treatment, the findings revealed a significant decline in miR-29 and miR-30b-5p gene expression and an increase in gene expression of Smad3, calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) isoforms, Matrix Metalloproteinases (MMPs), protein expression of TGF-β, heart tissue protein carbonyl and oxidized LDL (Ox-LDL), and plasma LDL and cholesterol levels in the CsA-treated group compared to the control group. The CsA group presented greater histological heart changes such as fibrosis, necrosis, hemorrhage, infiltrated leukocyte, and left ventricular weight/heart weight than the control group. Moreover, combined moderate exercise and CsA relatively improved gene expression changes and histological alternations compared to the CsA group.
Conclusion
TGF-β-Smad3-miR-29 and CaMKIIδ isoforms may mainly contribute to the progression of heart fibrosis and hypertrophy due to CsA exposure, providing new insight into the pathogenesis and treatment of CsA-induced side effects on the heart tissue. |
| doi_str_mv | 10.1007/s11033-023-08506-1 |
| format | Article |
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Cyclosporine A (CsA)-induced cardiac interstitial fibrosis and cardiac hypertrophy are highly known phenomena; however, the basic mechanisms of CsA cardiotoxicity are unclear. The present study evaluated the role of the Transforming growth factor-beta (TGF-β)/Smad3/miR-29b signaling pathway and CaMKIIδ isoforms gene expression in cardiac remodeling under CsA exposure alone or combined with moderate exercise.
Methods
A total of 24 male Wistar rats were divided into control, cyclosporine (30 mg/kg BW), and cyclosporine-exercise groups.
Results
After 42 days of treatment, the findings revealed a significant decline in miR-29 and miR-30b-5p gene expression and an increase in gene expression of Smad3, calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) isoforms, Matrix Metalloproteinases (MMPs), protein expression of TGF-β, heart tissue protein carbonyl and oxidized LDL (Ox-LDL), and plasma LDL and cholesterol levels in the CsA-treated group compared to the control group. The CsA group presented greater histological heart changes such as fibrosis, necrosis, hemorrhage, infiltrated leukocyte, and left ventricular weight/heart weight than the control group. Moreover, combined moderate exercise and CsA relatively improved gene expression changes and histological alternations compared to the CsA group.
Conclusion
TGF-β-Smad3-miR-29 and CaMKIIδ isoforms may mainly contribute to the progression of heart fibrosis and hypertrophy due to CsA exposure, providing new insight into the pathogenesis and treatment of CsA-induced side effects on the heart tissue.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-023-08506-1</identifier><identifier>PMID: 37231217</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Animal Anatomy ; Animal Biochemistry ; Biomedical and Life Sciences ; Calmodulin ; Cardiotoxicity ; Cholesterol ; Chromosome 5 ; Cyclosporins ; Fibrosis ; Gene expression ; Heart ; Hemorrhage ; Histology ; Hypertrophy ; Isoforms ; Life Sciences ; Low density lipoprotein ; Matrix metalloproteinase ; Morphology ; Original Article ; Proteins ; Signal transduction ; Smad3 protein ; Transforming growth factor-b ; Ventricle</subject><ispartof>Molecular biology reports, 2023-07, Vol.50 (7), p.5859-5870</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Nature B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-89f413b99026b1445666c891415f1d25b5363f5833377dea3bf6520e7de461613</cites><orcidid>0000-0002-3663-6823</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11033-023-08506-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-023-08506-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37231217$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nourmohammadi, Khatereh</creatorcontrib><creatorcontrib>Bayrami, Abolfazl</creatorcontrib><creatorcontrib>Naderi, Roya</creatorcontrib><creatorcontrib>Shirpoor, Alireza</creatorcontrib><title>Cyclosporine A induces cardiac remodeling through TGF-β/Smad3/miR-29 signaling pathway and alters gene expression of miR-30b-5p/CaMKIIδ isoforms pathways: alleviating effects of moderate exercise</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><addtitle>Mol Biol Rep</addtitle><description>Background
Cyclosporine A (CsA)-induced cardiac interstitial fibrosis and cardiac hypertrophy are highly known phenomena; however, the basic mechanisms of CsA cardiotoxicity are unclear. The present study evaluated the role of the Transforming growth factor-beta (TGF-β)/Smad3/miR-29b signaling pathway and CaMKIIδ isoforms gene expression in cardiac remodeling under CsA exposure alone or combined with moderate exercise.
Methods
A total of 24 male Wistar rats were divided into control, cyclosporine (30 mg/kg BW), and cyclosporine-exercise groups.
Results
After 42 days of treatment, the findings revealed a significant decline in miR-29 and miR-30b-5p gene expression and an increase in gene expression of Smad3, calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) isoforms, Matrix Metalloproteinases (MMPs), protein expression of TGF-β, heart tissue protein carbonyl and oxidized LDL (Ox-LDL), and plasma LDL and cholesterol levels in the CsA-treated group compared to the control group. The CsA group presented greater histological heart changes such as fibrosis, necrosis, hemorrhage, infiltrated leukocyte, and left ventricular weight/heart weight than the control group. Moreover, combined moderate exercise and CsA relatively improved gene expression changes and histological alternations compared to the CsA group.
Conclusion
TGF-β-Smad3-miR-29 and CaMKIIδ isoforms may mainly contribute to the progression of heart fibrosis and hypertrophy due to CsA exposure, providing new insight into the pathogenesis and treatment of CsA-induced side effects on the heart tissue.</description><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Calmodulin</subject><subject>Cardiotoxicity</subject><subject>Cholesterol</subject><subject>Chromosome 5</subject><subject>Cyclosporins</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Heart</subject><subject>Hemorrhage</subject><subject>Histology</subject><subject>Hypertrophy</subject><subject>Isoforms</subject><subject>Life Sciences</subject><subject>Low density lipoprotein</subject><subject>Matrix metalloproteinase</subject><subject>Morphology</subject><subject>Original Article</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Smad3 protein</subject><subject>Transforming growth factor-b</subject><subject>Ventricle</subject><issn>0301-4851</issn><issn>1573-4978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1u1DAURi0EokPhBVggS2zYmPFPHCfsqhEtI4qQoKwjJ7nJuEri4JsU5rUQr8C2z4Qz04LEgoVlSz7f8ZU_Qp4L_lpwbtYoBFeKcRlXpnnKxAOyEtooluQme0hWXHHBkkyLE_IE8ZpzngijH5MTZaQSUpgV-bXZV53H0Qc3AD2jbqjnCpBWNtTOVjRA72vo3NDSaRf83O7o1cU5u_2x_tzbWq1794nJnKJrB3ugRjvtvtk9tUNNbTdBQNpCVMP3MQCi8wP1DV1iipdMj-uN_fB-u739SR36xoce7xX4Jgo6uHF2WsTQNFBNeEjHkYKdFimEyiE8JY8a2yE8u9tPyZfzt1ebd-zy48V2c3bJKiXTiWV5kwhV5jmXaSmSRKdpWmW5SIRuRC11qVWqGp0ppYypwaqySbXkEM9JKlKhTsmro3cM_usMOBW9wwq6zg7gZyxkJjmXmisT0Zf_oNd-DvGTDlSWGyPyLFLySFXBIwZoijG43oZ9IXixlFwcSy5iycWh5GKZ4sWdei57qP9E7luNgDoCGK-GFsLft_-j_Q1HZ7PP</recordid><startdate>20230701</startdate><enddate>20230701</enddate><creator>Nourmohammadi, Khatereh</creator><creator>Bayrami, Abolfazl</creator><creator>Naderi, Roya</creator><creator>Shirpoor, Alireza</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3663-6823</orcidid></search><sort><creationdate>20230701</creationdate><title>Cyclosporine A induces cardiac remodeling through TGF-β/Smad3/miR-29 signaling pathway and alters gene expression of miR-30b-5p/CaMKIIδ isoforms pathways: alleviating effects of moderate exercise</title><author>Nourmohammadi, Khatereh ; 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Cyclosporine A (CsA)-induced cardiac interstitial fibrosis and cardiac hypertrophy are highly known phenomena; however, the basic mechanisms of CsA cardiotoxicity are unclear. The present study evaluated the role of the Transforming growth factor-beta (TGF-β)/Smad3/miR-29b signaling pathway and CaMKIIδ isoforms gene expression in cardiac remodeling under CsA exposure alone or combined with moderate exercise.
Methods
A total of 24 male Wistar rats were divided into control, cyclosporine (30 mg/kg BW), and cyclosporine-exercise groups.
Results
After 42 days of treatment, the findings revealed a significant decline in miR-29 and miR-30b-5p gene expression and an increase in gene expression of Smad3, calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) isoforms, Matrix Metalloproteinases (MMPs), protein expression of TGF-β, heart tissue protein carbonyl and oxidized LDL (Ox-LDL), and plasma LDL and cholesterol levels in the CsA-treated group compared to the control group. The CsA group presented greater histological heart changes such as fibrosis, necrosis, hemorrhage, infiltrated leukocyte, and left ventricular weight/heart weight than the control group. Moreover, combined moderate exercise and CsA relatively improved gene expression changes and histological alternations compared to the CsA group.
Conclusion
TGF-β-Smad3-miR-29 and CaMKIIδ isoforms may mainly contribute to the progression of heart fibrosis and hypertrophy due to CsA exposure, providing new insight into the pathogenesis and treatment of CsA-induced side effects on the heart tissue.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>37231217</pmid><doi>10.1007/s11033-023-08506-1</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3663-6823</orcidid></addata></record> |
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| subjects | Animal Anatomy Animal Biochemistry Biomedical and Life Sciences Calmodulin Cardiotoxicity Cholesterol Chromosome 5 Cyclosporins Fibrosis Gene expression Heart Hemorrhage Histology Hypertrophy Isoforms Life Sciences Low density lipoprotein Matrix metalloproteinase Morphology Original Article Proteins Signal transduction Smad3 protein Transforming growth factor-b Ventricle |
| title | Cyclosporine A induces cardiac remodeling through TGF-β/Smad3/miR-29 signaling pathway and alters gene expression of miR-30b-5p/CaMKIIδ isoforms pathways: alleviating effects of moderate exercise |
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