The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model
Diabetic cardiomyopathy (DCM) is pathologically characterized by excessive deposition of extracellular matrix proteins, leading to myocardial fibrosis. Fibromodulin (Fmod) plays a crucial role in the pathogenesis of fibrotic diseases. However, the role and mechanism of Fmod in DCM‐related myocardial...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13935 |
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| author | Xiyan Dai Fan Yang Dongping Chen Lu Yang Zhihui Dong Can Chen Jianmin Xiao |
| author_facet | Xiyan Dai Fan Yang Dongping Chen Lu Yang Zhihui Dong Can Chen Jianmin Xiao |
| author_sort | Xiyan Dai |
| collection | DOAJ |
| description | Diabetic cardiomyopathy (DCM) is pathologically characterized by excessive deposition of extracellular matrix proteins, leading to myocardial fibrosis. Fibromodulin (Fmod) plays a crucial role in the pathogenesis of fibrotic diseases. However, the role and mechanism of Fmod in DCM‐related myocardial fibrosis remain unclear. In the present study, we established a DCM rat model and an in vitro model of rat primary cardiac fibroblasts (RPCFs) exposed to high glucose. We assessed mRNA and protein expression levels of Col1a1, Col3a1, α‐SMA and Fmod in both models. Fmod‐overexpressing (ov‐Fmod) and Fmod‐knockdown (si‐Fmod) rat cardiac fibroblasts (RCFs) were generated. Subsequently, whole RNA sequencing was conducted on ov‐Fmod RCFs. The gene Col15a1 was evaluated in the DCM rat and all cell models. The correlation between plasma levels of Fmod and Col15a1 in DCM rat models was assessed. Transcription and protein levels of Fmod, Col1a1, Col3a1 and α‐SMA were significantly elevated in DCM rat hearts and RPCFs. In ov‐Fmod RCFs, fibrosis markers were similarly increased, except for Col3a1, which decreased. The Col1a1/Col3a1 ratio was elevated. Conversely, knocking down Fmod yielded opposite results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that Fmod participates in multiple fibrosis‐related pathways, affecting Col15a1. Expression of Col15a1 was significantly decreased in all models, compared to controls, except in si‐Fmod RCFs. Importantly, Col15a1 and Fmod in plasma exhibited an inverse relationship in DCM. In summary, Fmod is implicated in DCM, with Fmod overexpression downregulating Col15a1 and increasing the Col1a1/Col3a1 ratio. This mechanism may influence diastolic heart failure in DCM by modulating myocardial stiffness and elasticity. |
| format | Article |
| id | doaj-art-8160b9e635a04f2aa9386b56d8f76ddb |
| institution | DOAJ |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-8160b9e635a04f2aa9386b56d8f76ddb2025-08-20T02:58:00ZengWileyFEBS Open Bio2211-54632025-03-0115343644610.1002/2211-5463.13935The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat modelXiyan Dai0Fan Yang1Dongping Chen2Lu Yang3Zhihui Dong4Can Chen5Jianmin Xiao6Binhaiwan Central Hospital of Dongguan ChinaBinhaiwan Central Hospital of Dongguan ChinaBinhaiwan Central Hospital of Dongguan ChinaBinhaiwan Central Hospital of Dongguan ChinaBinhaiwan Central Hospital of Dongguan ChinaBinhaiwan Central Hospital of Dongguan ChinaBinhaiwan Central Hospital of Dongguan ChinaDiabetic cardiomyopathy (DCM) is pathologically characterized by excessive deposition of extracellular matrix proteins, leading to myocardial fibrosis. Fibromodulin (Fmod) plays a crucial role in the pathogenesis of fibrotic diseases. However, the role and mechanism of Fmod in DCM‐related myocardial fibrosis remain unclear. In the present study, we established a DCM rat model and an in vitro model of rat primary cardiac fibroblasts (RPCFs) exposed to high glucose. We assessed mRNA and protein expression levels of Col1a1, Col3a1, α‐SMA and Fmod in both models. Fmod‐overexpressing (ov‐Fmod) and Fmod‐knockdown (si‐Fmod) rat cardiac fibroblasts (RCFs) were generated. Subsequently, whole RNA sequencing was conducted on ov‐Fmod RCFs. The gene Col15a1 was evaluated in the DCM rat and all cell models. The correlation between plasma levels of Fmod and Col15a1 in DCM rat models was assessed. Transcription and protein levels of Fmod, Col1a1, Col3a1 and α‐SMA were significantly elevated in DCM rat hearts and RPCFs. In ov‐Fmod RCFs, fibrosis markers were similarly increased, except for Col3a1, which decreased. The Col1a1/Col3a1 ratio was elevated. Conversely, knocking down Fmod yielded opposite results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that Fmod participates in multiple fibrosis‐related pathways, affecting Col15a1. Expression of Col15a1 was significantly decreased in all models, compared to controls, except in si‐Fmod RCFs. Importantly, Col15a1 and Fmod in plasma exhibited an inverse relationship in DCM. In summary, Fmod is implicated in DCM, with Fmod overexpression downregulating Col15a1 and increasing the Col1a1/Col3a1 ratio. This mechanism may influence diastolic heart failure in DCM by modulating myocardial stiffness and elasticity.https://doi.org/10.1002/2211-5463.13935diabetic cardiomyopathyfibromodulinmyocardial fibrosis |
| spellingShingle | Xiyan Dai Fan Yang Dongping Chen Lu Yang Zhihui Dong Can Chen Jianmin Xiao The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model FEBS Open Bio diabetic cardiomyopathy fibromodulin myocardial fibrosis |
| title | The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model |
| title_full | The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model |
| title_fullStr | The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model |
| title_full_unstemmed | The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model |
| title_short | The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model |
| title_sort | role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model |
| topic | diabetic cardiomyopathy fibromodulin myocardial fibrosis |
| url | https://doi.org/10.1002/2211-5463.13935 |
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