Dynamic Interplay of Smooth Muscle α-Actin Gene-Regulatory Proteins Reflects the Biological Complexity of Myofibroblast Differentiation
Myofibroblasts (MFBs) are smooth muscle-like cells that provide contractile force required for tissue repair during wound healing. The leading agonist for MFB differentiation is transforming growth factor β1 (TGFβ1) that induces transcription of genes encoding smooth muscle α-actin (SMαA) and inters...
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| Format: | Article |
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MDPI AG
2013-03-01
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| Series: | Biology |
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| Online Access: | http://www.mdpi.com/2079-7737/2/2/555 |
| _version_ | 1797716802011136000 |
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| author | Seethalakshmi Hariharan Arthur Roger Strauch |
| author_facet | Seethalakshmi Hariharan Arthur Roger Strauch |
| author_sort | Seethalakshmi Hariharan |
| collection | DOAJ |
| description | Myofibroblasts (MFBs) are smooth muscle-like cells that provide contractile force required for tissue repair during wound healing. The leading agonist for MFB differentiation is transforming growth factor β1 (TGFβ1) that induces transcription of genes encoding smooth muscle α-actin (SMαA) and interstitial collagen that are markers for MFB differentiation. TGFβ1 augments activation of Smad transcription factors, pro-survival Akt kinase, and p38 MAP kinase as well as Wingless/int (Wnt) developmental signaling. These actions conspire to activate β-catenin needed for expression of cyclin D, laminin, fibronectin, and metalloproteinases that aid in repairing epithelial cells and their associated basement membranes. Importantly, β-catenin also provides a feed-forward stimulus that amplifies local TGFβ1 autocrine/paracrine signaling causing transition of mesenchymal stromal cells, pericytes, and epithelial cells into contractile MFBs. Complex, mutually interactive mechanisms have evolved that permit several mammalian cell types to activate the SMαA promoter and undergo MFB differentiation. These molecular controls will be reviewed with an emphasis on the dynamic interplay between serum response factor, TGFβ1-activated Smads, Wnt-activated β-catenin, p38/calcium-activated NFAT protein, and the RNA-binding proteins, Purα, Purβ, and YB-1, in governing transcriptional and translational control of the SMαA gene in injury-activated MFBs. |
| first_indexed | 2024-03-12T08:27:57Z |
| format | Article |
| id | doaj.art-96ad8b96d34647fa831ddf1f815317e7 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-12T08:27:57Z |
| publishDate | 2013-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-96ad8b96d34647fa831ddf1f815317e72023-09-02T18:00:47ZengMDPI AGBiology2079-77372013-03-012255558610.3390/biology2020555Dynamic Interplay of Smooth Muscle α-Actin Gene-Regulatory Proteins Reflects the Biological Complexity of Myofibroblast DifferentiationSeethalakshmi HariharanArthur Roger StrauchMyofibroblasts (MFBs) are smooth muscle-like cells that provide contractile force required for tissue repair during wound healing. The leading agonist for MFB differentiation is transforming growth factor β1 (TGFβ1) that induces transcription of genes encoding smooth muscle α-actin (SMαA) and interstitial collagen that are markers for MFB differentiation. TGFβ1 augments activation of Smad transcription factors, pro-survival Akt kinase, and p38 MAP kinase as well as Wingless/int (Wnt) developmental signaling. These actions conspire to activate β-catenin needed for expression of cyclin D, laminin, fibronectin, and metalloproteinases that aid in repairing epithelial cells and their associated basement membranes. Importantly, β-catenin also provides a feed-forward stimulus that amplifies local TGFβ1 autocrine/paracrine signaling causing transition of mesenchymal stromal cells, pericytes, and epithelial cells into contractile MFBs. Complex, mutually interactive mechanisms have evolved that permit several mammalian cell types to activate the SMαA promoter and undergo MFB differentiation. These molecular controls will be reviewed with an emphasis on the dynamic interplay between serum response factor, TGFβ1-activated Smads, Wnt-activated β-catenin, p38/calcium-activated NFAT protein, and the RNA-binding proteins, Purα, Purβ, and YB-1, in governing transcriptional and translational control of the SMαA gene in injury-activated MFBs.http://www.mdpi.com/2079-7737/2/2/555Myofibroblastgene transcriptionsmooth muscle actinwound healingfibrosis |
| spellingShingle | Seethalakshmi Hariharan Arthur Roger Strauch Dynamic Interplay of Smooth Muscle α-Actin Gene-Regulatory Proteins Reflects the Biological Complexity of Myofibroblast Differentiation Biology Myofibroblast gene transcription smooth muscle actin wound healing fibrosis |
| title | Dynamic Interplay of Smooth Muscle α-Actin Gene-Regulatory Proteins Reflects the Biological Complexity of Myofibroblast Differentiation |
| title_full | Dynamic Interplay of Smooth Muscle α-Actin Gene-Regulatory Proteins Reflects the Biological Complexity of Myofibroblast Differentiation |
| title_fullStr | Dynamic Interplay of Smooth Muscle α-Actin Gene-Regulatory Proteins Reflects the Biological Complexity of Myofibroblast Differentiation |
| title_full_unstemmed | Dynamic Interplay of Smooth Muscle α-Actin Gene-Regulatory Proteins Reflects the Biological Complexity of Myofibroblast Differentiation |
| title_short | Dynamic Interplay of Smooth Muscle α-Actin Gene-Regulatory Proteins Reflects the Biological Complexity of Myofibroblast Differentiation |
| title_sort | dynamic interplay of smooth muscle α actin gene regulatory proteins reflects the biological complexity of myofibroblast differentiation |
| topic | Myofibroblast gene transcription smooth muscle actin wound healing fibrosis |
| url | http://www.mdpi.com/2079-7737/2/2/555 |
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