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• W2897598897 abstract "Transthyretin (TTR)-related familial amyloid polyneuropathy (ATTR) results from aggregation and extracellular disposition of misfolded TTR mutants. Growing evidence suggests the importance of hepatic chaperones for the modulation of pathogenesis. We took advantage of induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from ATTR patients (ATTR-HLCs) to compare chaperone gene expression to that in HLCs from healthy individuals (H-HLCs). From the set of genes analyzed, chaperones that are predominantly located extracellularly were differently expressed. Expression of the chaperones showed a high correlation with TTR in both ATTR-HLCs and H-HLCs. In contrast, after TTR knockdown, the correlation was mainly affected in ATTR-HLCs suggesting that differences in TTR expression triggers aberrant chaperone expression. Serpin family A member 1 (SERPINA1) was the only extracellular chaperone that was markedly upregulated after TTR knockdown in ATTR-HLCs. Co-immunoprecipitation revealed that SERPINA1 physically interacts with TTR. In vitro assays indicated that SERPINA1 can interfere with TTR aggregation. Taken together, our results suggest that extracellular chaperones play a crucial role in ATTR pathogenesis, in particular SERPINA1, which may affect amyloid formation." @default.
• W2897598897 created "2018-10-26" @default.
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• W2897598897 date "2018-01-01" @default.
• W2897598897 modified "2023-10-16" @default.
• W2897598897 title "Hepatocyte-like cells reveal novel role of SerpinA1 in transthyretin amyloidosis" @default.
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• W2897598897 doi "https://doi.org/10.1242/jcs.219824" @default.
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