Human transthyretin gene expression is markedly increased in repair Schwann cells in an in vitro model of hereditary transthyretin amyloidosis

Hereditary transthyretin (TTR) amyloidosis (ATTRv) is characterized by TTR amyloid deposition in the peripheral nervous system. It remains unknown why variant TTR preferentially deposits in the peripheral nerves and dorsal root ganglia. We previously detected low levels of TTR expression in Schwann cells and established an immortalized Schwann cell line, TgS1, derived from a mouse model of ATTRv amyloidosis expressing the variant TTR gene. In the present study, the expression of TTR and Schwann cell marker genes was investigated in TgS1 cells by quantitative RT-PCR. TTR gene expression was markedly upregulated in TgS1 cells incubated in non-growth medium—Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. The expression levels of c-Jun, Gdnf and Sox2 were increased, while Mpz was downregulated, suggesting that TgS1 cells exhibit a repair Schwann cell-like phenotype in the non-growth medium. Western blot analysis revealed that TTR protein was produced and secreted by the TgS1 cells. Furthermore, downregulation of Hsf1 with siRNA induced TTR aggregates in the TgS1 cells. These findings indicate that TTR expression is markedly increased in repair Schwann cells, likely to promote axonal regeneration. Therefore, aged dysfunctional repair Schwann cells may cause the deposition of variant TTR aggregates in the nerves of patients with ATTRv. •We previously established a human TTR amyloidosis Schwann cell model, TgS1 cells.•TTR expression was markedly upregulated in TgS1 cells in non-growth medium.•The TgS1 cells exhibited a repair Schwann cell-like phenotype.•Downregulation of Hsf1 with siRNA resulted in variant TTR aggregates in TgS1 cells.•Schwann cells may be the source of TTR amyloid deposits in the nerve.