Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway
Abstract Keloids are a type of aberrant skin scarring characterized by excessive accumulation of collagen and extracellular matrix (ECM), arising from uncontrolled wound healing responses. While typically non-pathogenic, keloids are occasionally regarded as a form of benign tumor. CR6-interacting fa...
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| Format: | Article |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-79785-y |
| _version_ | 1818733740998787072 |
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| author | Harsha Nagar Sungmin Kim Ikjun Lee Seonhee Kim Su-Jeong Choi Shuyu Piao Byeong Hwa Jeon Sang-Ha Oh Cuk-Seong Kim |
| author_facet | Harsha Nagar Sungmin Kim Ikjun Lee Seonhee Kim Su-Jeong Choi Shuyu Piao Byeong Hwa Jeon Sang-Ha Oh Cuk-Seong Kim |
| author_sort | Harsha Nagar |
| collection | DOAJ |
| description | Abstract Keloids are a type of aberrant skin scarring characterized by excessive accumulation of collagen and extracellular matrix (ECM), arising from uncontrolled wound healing responses. While typically non-pathogenic, keloids are occasionally regarded as a form of benign tumor. CR6-interacting factor 1 (CRIF1) is a well-known CR6/GADD45-interacting protein, that has both nuclear and mitochondrial functions, and also exerts regulatory effects on cell growth and apoptosis. In this study, cell proliferation, cell migration, collagen production and TGF-β signaling was compared between normal fibroblasts (NFs) and keloid fibroblasts (KFs). Subsequently, the effects of CRIF1 deficiency were investigated in both NFs and KFs. Cell proliferation, cell migration, collagen production and protein expressions of TGF-β, phosphorylation of Smad2 and Smad3 were all found to be higher in KFs compared to NFs. CRIF1 deficiency in NFs and KFs inhibited cell proliferation, migration, and collagen production. In addition, phosphorylation of Smad2 and Smad3, which are transcription factors of collagen, was decreased. In contrast, mRNA expression levels of Smad7 and SMURF2, two important inhibitory proteins of Smad2/3, were increased, suggesting that CRIF1 may regulate collagen production. CRIF1 deficiency decreases the proliferation and migration of KFs, thereby inhibiting their overgrowth via the transforming growth factor-β (TGF-β)/Smad pathway. CRIF1 may therefore represent a potential therapeutic target in keloid pathogenesis. |
| first_indexed | 2024-12-17T23:54:17Z |
| format | Article |
| id | doaj.art-222206fa63144f6094cdf0776c494714 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T23:54:17Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-222206fa63144f6094cdf0776c4947142022-12-21T21:28:06ZengNature PortfolioScientific Reports2045-23222021-01-0111111310.1038/s41598-020-79785-yDownregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathwayHarsha Nagar0Sungmin Kim1Ikjun Lee2Seonhee Kim3Su-Jeong Choi4Shuyu Piao5Byeong Hwa Jeon6Sang-Ha Oh7Cuk-Seong Kim8Department of Medical Science, Chungnam National UniversityDepartment of Medical Science, Chungnam National UniversityDepartment of Medical Science, Chungnam National UniversityDepartment of Medical Science, Chungnam National UniversityDepartment of Medical Science, Chungnam National UniversityDepartment of Medical Science, Chungnam National UniversityDepartment of Medical Science, Chungnam National UniversityDepartment of Plastic and Reconstructive Surgery, School of Medicine, Chungnam National UniversityDepartment of Medical Science, Chungnam National UniversityAbstract Keloids are a type of aberrant skin scarring characterized by excessive accumulation of collagen and extracellular matrix (ECM), arising from uncontrolled wound healing responses. While typically non-pathogenic, keloids are occasionally regarded as a form of benign tumor. CR6-interacting factor 1 (CRIF1) is a well-known CR6/GADD45-interacting protein, that has both nuclear and mitochondrial functions, and also exerts regulatory effects on cell growth and apoptosis. In this study, cell proliferation, cell migration, collagen production and TGF-β signaling was compared between normal fibroblasts (NFs) and keloid fibroblasts (KFs). Subsequently, the effects of CRIF1 deficiency were investigated in both NFs and KFs. Cell proliferation, cell migration, collagen production and protein expressions of TGF-β, phosphorylation of Smad2 and Smad3 were all found to be higher in KFs compared to NFs. CRIF1 deficiency in NFs and KFs inhibited cell proliferation, migration, and collagen production. In addition, phosphorylation of Smad2 and Smad3, which are transcription factors of collagen, was decreased. In contrast, mRNA expression levels of Smad7 and SMURF2, two important inhibitory proteins of Smad2/3, were increased, suggesting that CRIF1 may regulate collagen production. CRIF1 deficiency decreases the proliferation and migration of KFs, thereby inhibiting their overgrowth via the transforming growth factor-β (TGF-β)/Smad pathway. CRIF1 may therefore represent a potential therapeutic target in keloid pathogenesis.https://doi.org/10.1038/s41598-020-79785-y |
| spellingShingle | Harsha Nagar Sungmin Kim Ikjun Lee Seonhee Kim Su-Jeong Choi Shuyu Piao Byeong Hwa Jeon Sang-Ha Oh Cuk-Seong Kim Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway Scientific Reports |
| title | Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway |
| title_full | Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway |
| title_fullStr | Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway |
| title_full_unstemmed | Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway |
| title_short | Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway |
| title_sort | downregulation of cr6 interacting factor 1 suppresses keloid fibroblast growth via the tgf β smad signaling pathway |
| url | https://doi.org/10.1038/s41598-020-79785-y |
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