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SERPINA1 modulates expression of amyloidogenic transthyretin

Exp Cell Res. 2020; 
Christoph Niemietz, Filipa Bezerra, Maria Rosário Almeida, Shuling Guo, Brett P Monia, Maria João Saraiva, Paula Schütz, Hartmut H-J Schmidt, Andree Zibert
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Recombinant Antibody Expression … PBS was used as control. OSM treatment was for up to 72 h with daily media change. Animal studies: V30 M mice at the age of 5–7 months received mouse recombinant OSM (Z03143, Genscript) by intraperitoneal (ip) injection. PBS was used as control … Get A Quote

摘要

Hereditary transthyretin amyloidosis (ATTR) is caused by amyloid deposition of misfolded transthyretin (TTR) in various tissues. Recently, reduction of circulating serum TTR, achieved via silencing oligonucleotides, was introduced as therapy of ATTR amyloidosis. We explored the impact of Serpin Family A Member 1 (SERPINA1) on TTR mRNA and protein expression. Oncostatin M (OSM) induced SERPINA1 in hepatoma cells and mice, while concomitantly TTR expression was significantly reduced. SERPINA1 knockdown resulted in specific elevated TTR expression in hepatoma cells; however other genes belonging to the group of acute phase proteins were unaffected. In mice, serum TTR was elevated after mSERPINA1 knockdown througho... More

关键词

ATTR amyloidosis, Alpha-1-antitrypsin, Antisense oligonucleotide, Disease modeling, Oncostatin M