MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis
MicroRNAs (miRNAs) are well-known candidates for modulating the dysregulated signaling pathways during fibrosis. In this study, we investigated the expression pattern of 16 miRNAs, which have previously been confirmed or predicted to target genes involved in extracellular matrix (ECM) homeostasis. P...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-04-01
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| Series: | Autoimmunity |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08916934.2019.1621856 |
| _version_ | 1827817433240436736 |
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| author | Saeideh Jafarinejad-Farsangi Farhad Gharibdoost Ali Farazmand Hoda Kavosi Ahmadreza Jamshidi Elham Karimizadeh Farshid Noorbakhsh Mahdi Mahmoudi |
| author_facet | Saeideh Jafarinejad-Farsangi Farhad Gharibdoost Ali Farazmand Hoda Kavosi Ahmadreza Jamshidi Elham Karimizadeh Farshid Noorbakhsh Mahdi Mahmoudi |
| author_sort | Saeideh Jafarinejad-Farsangi |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) are well-known candidates for modulating the dysregulated signaling pathways during fibrosis. In this study, we investigated the expression pattern of 16 miRNAs, which have previously been confirmed or predicted to target genes involved in extracellular matrix (ECM) homeostasis. Primary culture of dermal fibroblasts was obtained from skin biopsies of diffused cutaneous SSc (dcSSc) patients and healthy controls. Expression of let-7a, miR-1, miR-15a, miR-17, miR-19a, miR-20a, miR-21, miR-27b, miR-26a, miR-29a, miR-29b, miR29c, miR-141, miR-125a-5p, miR-193a-3p, and miR-200a were quantified by Real-time PCR. Functional analysis of microRNAs was performed using synthetic oligonucleotides. To further confirm the pro- or anti-fibrotic effects of miRNAs, normal fibroblasts were treated with 10 ng/mL of transforming growth factor (TGF)-β to generate an in vitro model of dermal fibrosis. miR-21 and miR-29a were upregulated and downregulated, respectively, in both dcSSc and TGF-β-treated fibroblasts. We observed that restoration of miR-29a expression or blockade of miR-21 function negatively affected collagen production. COL1A1 expression in SSc fibroblasts is more sensitive to changes of miR-29a and miR-21 expression in compare to normal fibroblasts. miR-29a alone was effective to decrease TGF-β-induced collagen production in dermal fibroblasts. miR-21 and TGF-β had synergistic effects on induction of collagen production. However, neither miR-21 nor miR-29a affected alpha smooth muscle actin (α-SMA) expression in the presence or absence of TGF-β in dermal fibroblasts. miR-21 and miR-29a as pro- and anti-fibrotic miRNAs modulate collagen production in an opposing manner. Focusing on miR-21 and miR-29s as therapeutic targets would be effective in patients with SSc or other fibrotic diseases which show aberrant expression of collagen expression. |
| first_indexed | 2024-03-12T00:34:13Z |
| format | Article |
| id | doaj.art-8784cdfe3c8c45ac91a965e45497454e |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:34:13Z |
| publishDate | 2019-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-8784cdfe3c8c45ac91a965e45497454e2023-09-15T10:01:08ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2019-04-0152310811610.1080/08916934.2019.16218561621856MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosisSaeideh Jafarinejad-Farsangi0Farhad Gharibdoost1Ali Farazmand2Hoda Kavosi3Ahmadreza Jamshidi4Elham Karimizadeh5Farshid Noorbakhsh6Mahdi Mahmoudi7Kerman University of Medical SciencesTehran University of Medical SciencesUniversity of TehranTehran University of Medical SciencesTehran University of Medical SciencesTehran University of Medical SciencesTehran University of Medical SciencesTehran University of Medical SciencesMicroRNAs (miRNAs) are well-known candidates for modulating the dysregulated signaling pathways during fibrosis. In this study, we investigated the expression pattern of 16 miRNAs, which have previously been confirmed or predicted to target genes involved in extracellular matrix (ECM) homeostasis. Primary culture of dermal fibroblasts was obtained from skin biopsies of diffused cutaneous SSc (dcSSc) patients and healthy controls. Expression of let-7a, miR-1, miR-15a, miR-17, miR-19a, miR-20a, miR-21, miR-27b, miR-26a, miR-29a, miR-29b, miR29c, miR-141, miR-125a-5p, miR-193a-3p, and miR-200a were quantified by Real-time PCR. Functional analysis of microRNAs was performed using synthetic oligonucleotides. To further confirm the pro- or anti-fibrotic effects of miRNAs, normal fibroblasts were treated with 10 ng/mL of transforming growth factor (TGF)-β to generate an in vitro model of dermal fibrosis. miR-21 and miR-29a were upregulated and downregulated, respectively, in both dcSSc and TGF-β-treated fibroblasts. We observed that restoration of miR-29a expression or blockade of miR-21 function negatively affected collagen production. COL1A1 expression in SSc fibroblasts is more sensitive to changes of miR-29a and miR-21 expression in compare to normal fibroblasts. miR-29a alone was effective to decrease TGF-β-induced collagen production in dermal fibroblasts. miR-21 and TGF-β had synergistic effects on induction of collagen production. However, neither miR-21 nor miR-29a affected alpha smooth muscle actin (α-SMA) expression in the presence or absence of TGF-β in dermal fibroblasts. miR-21 and miR-29a as pro- and anti-fibrotic miRNAs modulate collagen production in an opposing manner. Focusing on miR-21 and miR-29s as therapeutic targets would be effective in patients with SSc or other fibrotic diseases which show aberrant expression of collagen expression.http://dx.doi.org/10.1080/08916934.2019.1621856micrornamir-21mir-29afibrosiscollagensystemic sclerosis |
| spellingShingle | Saeideh Jafarinejad-Farsangi Farhad Gharibdoost Ali Farazmand Hoda Kavosi Ahmadreza Jamshidi Elham Karimizadeh Farshid Noorbakhsh Mahdi Mahmoudi MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis Autoimmunity microrna mir-21 mir-29a fibrosis collagen systemic sclerosis |
| title | MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis |
| title_full | MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis |
| title_fullStr | MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis |
| title_full_unstemmed | MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis |
| title_short | MicroRNA-21 and microRNA-29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis |
| title_sort | microrna 21 and microrna 29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis |
| topic | microrna mir-21 mir-29a fibrosis collagen systemic sclerosis |
| url | http://dx.doi.org/10.1080/08916934.2019.1621856 |
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