High-content Image-based Drug Testing of Patients’ Primary Fibroblasts Reveals Potential New Treatment Options for Localized Scleroderma
Localized scleroderma is a rare autoimmune disease characterized by progressive fibrosis of the skin and its underlying structures, causing loss of normal tissue structure and function. Myofibroblasts, differentiated from fibroblasts by high expression of α-smooth muscle actin, play a key role in th...
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Medical Journals Sweden
2025-08-01
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| Series: | Acta Dermato-Venereologica |
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| Online Access: | https://medicaljournalssweden.se/actadv/article/view/43088 |
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| author | Katariina Mähönen Isabel Mogollon Antti Hassinen Minttu Polso Katja Välimäki Swapnil Potdar Al-Amin Chowdhury Annamari Ranki Jani Saarela Vilja Pietiäinen Jaana Panelius |
| author_facet | Katariina Mähönen Isabel Mogollon Antti Hassinen Minttu Polso Katja Välimäki Swapnil Potdar Al-Amin Chowdhury Annamari Ranki Jani Saarela Vilja Pietiäinen Jaana Panelius |
| author_sort | Katariina Mähönen |
| collection | DOAJ |
| description | Localized scleroderma is a rare autoimmune disease characterized by progressive fibrosis of the skin and its underlying structures, causing loss of normal tissue structure and function. Myofibroblasts, differentiated from fibroblasts by high expression of α-smooth muscle actin, play a key role in the pathogenesis with continuous production of collagen and other extracellular matrix components. Transforming growth factor β promotes myofibroblast transformation and is central to the pathogenesis of fibrotic diseases. Targeted therapies for skin fibrosis are lacking, and current treatment consisting of topical steroids and immunosuppressive drugs often has limited efficacy. In this study, testing was performed with 78 drugs on lesional localized scleroderma fibroblasts to find potential new therapies, with α-smooth muscle actin and collagen-1 expression as markers for antifibrotic effect. Several drugs belonging to inhibitors of tyrosine kinase, phosphoinositide-3 kinase, and transforming growth factor β receptor were found to have an antifibrotic effect in localized scleroderma fibroblasts. Along with increased expression of transforming growth factor β1, Smad3, and AKT found in lesional localized scleroderma skin, these results confirm transforming growth factor β pathway as a treatment target. Additionally, androgen receptor antagonists showed potential antifibrotic effects, co-aligning with an increased expression of androgen receptor in localized scleroderma skin.
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| format | Article |
| id | doaj-art-aaccce4a7e6e4e419d4649740e7011db |
| institution | Kabale University |
| issn | 0001-5555 1651-2057 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Medical Journals Sweden |
| record_format | Article |
| series | Acta Dermato-Venereologica |
| spelling | doaj-art-aaccce4a7e6e4e419d4649740e7011db2025-08-20T03:37:09ZengMedical Journals SwedenActa Dermato-Venereologica0001-55551651-20572025-08-0110510.2340/actadv.v105.43088High-content Image-based Drug Testing of Patients’ Primary Fibroblasts Reveals Potential New Treatment Options for Localized SclerodermaKatariina Mähönen0Isabel Mogollon1Antti Hassinen2Minttu Polso3Katja Välimäki4Swapnil Potdar5Al-Amin Chowdhury6Annamari Ranki7Jani Saarela8Vilja Pietiäinen9Jaana Panelius10epartment of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandInstitute for Molecular Medicine Finland – FIMM, Helsinki Institute for Life Sciences – HiLIFE, University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland – FIMM, Helsinki Institute for Life Sciences – HiLIFE, University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland – FIMM, Helsinki Institute for Life Sciences – HiLIFE, University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland – FIMM, Helsinki Institute for Life Sciences – HiLIFE, University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland – FIMM, Helsinki Institute for Life Sciences – HiLIFE, University of Helsinki, Helsinki, Finlandepartment of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finlandepartment of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandInstitute for Molecular Medicine Finland – FIMM, Helsinki Institute for Life Sciences – HiLIFE, University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland – FIMM, Helsinki Institute for Life Sciences – HiLIFE, University of Helsinki, Helsinki, Finlandepartment of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandLocalized scleroderma is a rare autoimmune disease characterized by progressive fibrosis of the skin and its underlying structures, causing loss of normal tissue structure and function. Myofibroblasts, differentiated from fibroblasts by high expression of α-smooth muscle actin, play a key role in the pathogenesis with continuous production of collagen and other extracellular matrix components. Transforming growth factor β promotes myofibroblast transformation and is central to the pathogenesis of fibrotic diseases. Targeted therapies for skin fibrosis are lacking, and current treatment consisting of topical steroids and immunosuppressive drugs often has limited efficacy. In this study, testing was performed with 78 drugs on lesional localized scleroderma fibroblasts to find potential new therapies, with α-smooth muscle actin and collagen-1 expression as markers for antifibrotic effect. Several drugs belonging to inhibitors of tyrosine kinase, phosphoinositide-3 kinase, and transforming growth factor β receptor were found to have an antifibrotic effect in localized scleroderma fibroblasts. Along with increased expression of transforming growth factor β1, Smad3, and AKT found in lesional localized scleroderma skin, these results confirm transforming growth factor β pathway as a treatment target. Additionally, androgen receptor antagonists showed potential antifibrotic effects, co-aligning with an increased expression of androgen receptor in localized scleroderma skin. https://medicaljournalssweden.se/actadv/article/view/43088Localized sclerodermaMyofibroblaststransforming growth factor betaantifibrotic agentshigh throughput screening assay |
| spellingShingle | Katariina Mähönen Isabel Mogollon Antti Hassinen Minttu Polso Katja Välimäki Swapnil Potdar Al-Amin Chowdhury Annamari Ranki Jani Saarela Vilja Pietiäinen Jaana Panelius High-content Image-based Drug Testing of Patients’ Primary Fibroblasts Reveals Potential New Treatment Options for Localized Scleroderma Acta Dermato-Venereologica Localized scleroderma Myofibroblasts transforming growth factor beta antifibrotic agents high throughput screening assay |
| title | High-content Image-based Drug Testing of Patients’ Primary Fibroblasts Reveals Potential New Treatment Options for Localized Scleroderma |
| title_full | High-content Image-based Drug Testing of Patients’ Primary Fibroblasts Reveals Potential New Treatment Options for Localized Scleroderma |
| title_fullStr | High-content Image-based Drug Testing of Patients’ Primary Fibroblasts Reveals Potential New Treatment Options for Localized Scleroderma |
| title_full_unstemmed | High-content Image-based Drug Testing of Patients’ Primary Fibroblasts Reveals Potential New Treatment Options for Localized Scleroderma |
| title_short | High-content Image-based Drug Testing of Patients’ Primary Fibroblasts Reveals Potential New Treatment Options for Localized Scleroderma |
| title_sort | high content image based drug testing of patients primary fibroblasts reveals potential new treatment options for localized scleroderma |
| topic | Localized scleroderma Myofibroblasts transforming growth factor beta antifibrotic agents high throughput screening assay |
| url | https://medicaljournalssweden.se/actadv/article/view/43088 |
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