Fusion protein of retinol‐binding protein and albumin domain III reduces liver fibrosis
Abstract Activated hepatic stellate cells (HSCs) play a key role in liver fibrosis, and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin and its derivative designed for stellate cell‐targeting, retinol‐binding protein–albumin domain III fusion...
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| Format: | Article |
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Springer Nature
2015-04-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201404527 |
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| author | Hongsik Lee Hyeyeun Jeong Sangeun Park Wonbaek Yoo Soyoung Choi Kyungmin Choi Min‐Goo Lee Mihwa Lee DaeRyong Cha Young‐Sik Kim Jeeyoung Han Wonkon Kim Sun‐Hwa Park Junseo Oh |
| author_facet | Hongsik Lee Hyeyeun Jeong Sangeun Park Wonbaek Yoo Soyoung Choi Kyungmin Choi Min‐Goo Lee Mihwa Lee DaeRyong Cha Young‐Sik Kim Jeeyoung Han Wonkon Kim Sun‐Hwa Park Junseo Oh |
| author_sort | Hongsik Lee |
| collection | DOAJ |
| description | Abstract Activated hepatic stellate cells (HSCs) play a key role in liver fibrosis, and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin and its derivative designed for stellate cell‐targeting, retinol‐binding protein–albumin domain III fusion protein (referred to as R‐III), inactivate cultured HSCs. Here, we investigated the mechanism of action of albumin/R‐III in HSCs and examined the anti‐fibrotic potential of R‐III in vivo. R‐III treatment and albumin expression downregulated retinoic acid (RA) signaling which was involved in HSC activation. RA receptor agonist and retinaldehyde dehydrogenase overexpression abolished the anti‐fibrotic effect of R‐III and albumin, respectively. R‐III uptake into cultured HSCs was significantly decreased by siRNA‐STRA6, and injected R‐III was localized predominantly in HSCs in liver. Importantly, R‐III administration reduced CCl4‐ and bile duct ligation‐induced liver fibrosis. R‐III also exhibited a preventive effect against CCl4‐inducd liver fibrosis. These findings suggest that the anti‐fibrotic effect of albumin/R‐III is, at least in part, mediated by downregulation of RA signaling and that R‐III is a good candidate as a novel anti‐fibrotic drug. |
| format | Article |
| id | doaj-art-0064c9599aaa4cbbb6dd48df0f533c34 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2015-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-0064c9599aaa4cbbb6dd48df0f533c342025-08-20T04:02:56ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842015-04-017681983010.15252/emmm.201404527Fusion protein of retinol‐binding protein and albumin domain III reduces liver fibrosisHongsik Lee0Hyeyeun Jeong1Sangeun Park2Wonbaek Yoo3Soyoung Choi4Kyungmin Choi5Min‐Goo Lee6Mihwa Lee7DaeRyong Cha8Young‐Sik Kim9Jeeyoung Han10Wonkon Kim11Sun‐Hwa Park12Junseo Oh13Department of Internal Medicine, College of Medicine, Korea UniversityDepartment of Anatomy, College of Medicine, Korea UniversityDepartment of Anatomy, College of Medicine, Korea UniversityDepartment of Anatomy, College of Medicine, Korea UniversityDepartment of Anatomy, College of Medicine, Korea UniversityDepartment of Physiology, College of Medicine, Korea UniversityDepartment of Physiology, College of Medicine, Korea UniversityDepartment of Nephrology, College of Medicine, Korea UniversityDepartment of Nephrology, College of Medicine, Korea UniversityDepartment of Pathology, College of Medicine, Korea UniversityDepartment of Pathology, Inha University HospitalMedical Proteomics Research Center, KRIBBDepartment of Anatomy, College of Medicine, Korea UniversityDepartment of Anatomy, College of Medicine, Korea UniversityAbstract Activated hepatic stellate cells (HSCs) play a key role in liver fibrosis, and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin and its derivative designed for stellate cell‐targeting, retinol‐binding protein–albumin domain III fusion protein (referred to as R‐III), inactivate cultured HSCs. Here, we investigated the mechanism of action of albumin/R‐III in HSCs and examined the anti‐fibrotic potential of R‐III in vivo. R‐III treatment and albumin expression downregulated retinoic acid (RA) signaling which was involved in HSC activation. RA receptor agonist and retinaldehyde dehydrogenase overexpression abolished the anti‐fibrotic effect of R‐III and albumin, respectively. R‐III uptake into cultured HSCs was significantly decreased by siRNA‐STRA6, and injected R‐III was localized predominantly in HSCs in liver. Importantly, R‐III administration reduced CCl4‐ and bile duct ligation‐induced liver fibrosis. R‐III also exhibited a preventive effect against CCl4‐inducd liver fibrosis. These findings suggest that the anti‐fibrotic effect of albumin/R‐III is, at least in part, mediated by downregulation of RA signaling and that R‐III is a good candidate as a novel anti‐fibrotic drug.https://doi.org/10.15252/emmm.201404527albuminanti‐fibrotic drugfibrosishepatic stellate cellretinoic acid |
| spellingShingle | Hongsik Lee Hyeyeun Jeong Sangeun Park Wonbaek Yoo Soyoung Choi Kyungmin Choi Min‐Goo Lee Mihwa Lee DaeRyong Cha Young‐Sik Kim Jeeyoung Han Wonkon Kim Sun‐Hwa Park Junseo Oh Fusion protein of retinol‐binding protein and albumin domain III reduces liver fibrosis EMBO Molecular Medicine albumin anti‐fibrotic drug fibrosis hepatic stellate cell retinoic acid |
| title | Fusion protein of retinol‐binding protein and albumin domain III reduces liver fibrosis |
| title_full | Fusion protein of retinol‐binding protein and albumin domain III reduces liver fibrosis |
| title_fullStr | Fusion protein of retinol‐binding protein and albumin domain III reduces liver fibrosis |
| title_full_unstemmed | Fusion protein of retinol‐binding protein and albumin domain III reduces liver fibrosis |
| title_short | Fusion protein of retinol‐binding protein and albumin domain III reduces liver fibrosis |
| title_sort | fusion protein of retinol binding protein and albumin domain iii reduces liver fibrosis |
| topic | albumin anti‐fibrotic drug fibrosis hepatic stellate cell retinoic acid |
| url | https://doi.org/10.15252/emmm.201404527 |
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