Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosis
Hereditary transthyretin (TTR) amyloidosis (ATTRv amyloidosis) is an autosomal dominant disease caused by various TTR mutations. Despite the fact that ATTR Tyr114Cys (p.Tyr134Cys) amyloidosis (tyrosine to cysteine at codon 114) exhibits poorer prognosis than other ATTRv amyloidosis and leads to deat...
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Elsevier
2025-06-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825000998 |
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| author | Kenta Ouchi Takeshi Masuda Kou Yonemaru Kaori Isono Yuki Ohya Nobuaki Shiraki Masayoshi Tasaki Yukihiro Inomata Mitsuharu Ueda Takumi Era Shoen Kume Yukio Ando Hirofumi Jono |
| author_facet | Kenta Ouchi Takeshi Masuda Kou Yonemaru Kaori Isono Yuki Ohya Nobuaki Shiraki Masayoshi Tasaki Yukihiro Inomata Mitsuharu Ueda Takumi Era Shoen Kume Yukio Ando Hirofumi Jono |
| author_sort | Kenta Ouchi |
| collection | DOAJ |
| description | Hereditary transthyretin (TTR) amyloidosis (ATTRv amyloidosis) is an autosomal dominant disease caused by various TTR mutations. Despite the fact that ATTR Tyr114Cys (p.Tyr134Cys) amyloidosis (tyrosine to cysteine at codon 114) exhibits poorer prognosis than other ATTRv amyloidosis and leads to death due to severe clinical symptoms, the molecular pathogenesis of ATTR Tyr114Cys amyloidosis is still largely unknown. In this study, we took advantage of ATTR Tyr114Cys amyloidosis-specific induced pluripotent stem (iPS) cells to differentiate into hepatocyte-like cells (Y114C-HLCs), which are mainly TTR producing cells, and elucidated their pathogenesis. We performed proteomic analysis to comprehensively identify specific intracellular signaling pathways involved in Y114C-HLCs, and identified the specific proteins changed only in Y114C-HLCs, in comparison with disease control HLCs from ATTR Val30Met amyloidosis (V30M-HLCs). Moreover, we have succeeded in identifying several specific intracellular signals that are significantly activated in Y114C-HLCs, including cellular responses to stress and extracellular matrix organization. Our proteomic analysis is the first to report that the specific point mutations in ATTRv amyloidosis cause dynamic changes in cellular response, and reveal the specific intracellular signals may be involved in the specific pathogenesis of ATTR Tyr114Cys amyloidosis. |
| format | Article |
| id | doaj-art-3f9b2bdb647e42aa9bf668eb2c19b283 |
| institution | OA Journals |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-3f9b2bdb647e42aa9bf668eb2c19b2832025-08-20T02:17:09ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210201210.1016/j.bbrep.2025.102012Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosisKenta Ouchi0Takeshi Masuda1Kou Yonemaru2Kaori Isono3Yuki Ohya4Nobuaki Shiraki5Masayoshi Tasaki6Yukihiro Inomata7Mitsuharu Ueda8Takumi Era9Shoen Kume10Yukio Ando11Hirofumi Jono12Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, JapanGraduate School of Media and Governance / Institute for Advanced Biosciences, Keio University, 14-1 Baba-machi, Tsuruoka-City, Yamagata Prefecture, 997-0035, JapanDepartment of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, JapanDepartment of Transplantation and Paediatric Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, JapanDepartment of Transplantation and Paediatric Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, Japan; Department of Pediatric Surgery, Kumamoto Rosai Hospital, 1670 Takehara-cho, Yatsushiro City, Kumamoto Prefecture, 866-0826, JapanSchool of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori Ward, Yokohama City, Kanagawa Prefecture, 226-8501, JapanDepartment of Biomedical Laboratory Sciences, Graduate School of Health Sciences, Kumamoto University, Kumamoto, 1-1-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, Japan; Department of Neurology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, JapanDepartment of Pediatric Surgery, Kumamoto Rosai Hospital, 1670 Takehara-cho, Yatsushiro City, Kumamoto Prefecture, 866-0826, JapanDepartment of Neurology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, JapanDepartment of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, JapanSchool of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori Ward, Yokohama City, Kanagawa Prefecture, 226-8501, JapanDepartment of Amyloidosis Research, Nagasaki International University, 2825-7 Huis Ten Bosch Cho, Sasebo City, Nagasaki Prefecture, 859-3298, JapanDepartment of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, Japan; Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, Japan; Corresponding author. Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto Prefecture, 860-8556, Japan.Hereditary transthyretin (TTR) amyloidosis (ATTRv amyloidosis) is an autosomal dominant disease caused by various TTR mutations. Despite the fact that ATTR Tyr114Cys (p.Tyr134Cys) amyloidosis (tyrosine to cysteine at codon 114) exhibits poorer prognosis than other ATTRv amyloidosis and leads to death due to severe clinical symptoms, the molecular pathogenesis of ATTR Tyr114Cys amyloidosis is still largely unknown. In this study, we took advantage of ATTR Tyr114Cys amyloidosis-specific induced pluripotent stem (iPS) cells to differentiate into hepatocyte-like cells (Y114C-HLCs), which are mainly TTR producing cells, and elucidated their pathogenesis. We performed proteomic analysis to comprehensively identify specific intracellular signaling pathways involved in Y114C-HLCs, and identified the specific proteins changed only in Y114C-HLCs, in comparison with disease control HLCs from ATTR Val30Met amyloidosis (V30M-HLCs). Moreover, we have succeeded in identifying several specific intracellular signals that are significantly activated in Y114C-HLCs, including cellular responses to stress and extracellular matrix organization. Our proteomic analysis is the first to report that the specific point mutations in ATTRv amyloidosis cause dynamic changes in cellular response, and reveal the specific intracellular signals may be involved in the specific pathogenesis of ATTR Tyr114Cys amyloidosis.http://www.sciencedirect.com/science/article/pii/S2405580825000998ATTR amyloidosisTransthyretinInduced pluripotent stem cellsProteomic analysis |
| spellingShingle | Kenta Ouchi Takeshi Masuda Kou Yonemaru Kaori Isono Yuki Ohya Nobuaki Shiraki Masayoshi Tasaki Yukihiro Inomata Mitsuharu Ueda Takumi Era Shoen Kume Yukio Ando Hirofumi Jono Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosis Biochemistry and Biophysics Reports ATTR amyloidosis Transthyretin Induced pluripotent stem cells Proteomic analysis |
| title | Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosis |
| title_full | Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosis |
| title_fullStr | Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosis |
| title_full_unstemmed | Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosis |
| title_short | Dynamic changes of intracellular signals in ATTR Tyr114Cys amyloidosis |
| title_sort | dynamic changes of intracellular signals in attr tyr114cys amyloidosis |
| topic | ATTR amyloidosis Transthyretin Induced pluripotent stem cells Proteomic analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825000998 |
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