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. 2020 Apr 6;13(4):dmm042911. doi: 10.1242/dmm.042911

Fig. 3.

Fig. 3.

Rosuvastatin increases total LDLR protein levels and an accumulation of immature LDLR in NC cells. (A) PSC were treated overnight in LPDS medium supplemented with either lovastatin (Lova), rosuvastatin (RS) or excess sterols (XS). Western blot analysis for LDLR shows that NC-iPSC upregulate immature LDLR in Lova, whereas C-iPSC and H1-ESC express mature LDLR. RS treatment produces the same response, and LDLR is suppressed when exposed to sterols. Recombinant human LDLR protein (rhLDLR) was used as a detection control. (B) Quantification of total LDLR demonstrated that RS-treated NC-iPSC had a significantly greater total LDLR than C-iPSC and H1-ESC treated with RS. All three statin-treated cell types were significantly greater compared to their XS-treated counterparts. (C) iPSC/ESC were differentiated to HLC. Under the same conditions of rosuvastatin RS or XS treatment, NC-HLC express greater total LDLR, predominantly as immature protein, which is converted to all mature protein in C-HLC and H1-HLC. LDLR levels decreased with sterol treatment. (D) Two-way ANOVA analysis of total LDLR in HLC indicated a significant difference in mean between cell types and in response to RS treatment. Total LDLR in RS-treated NC cells was statistically different from that in RS-treated C and H1 cells. As expected, for each cell type, total LDLR was significantly different when comparing RS and XS treatments. (E) qPCR quantification of LDLR mRNA shows that RS treatment significantly increases LDLR transcript levels in NC-iPSC, C-iPSC and H1-ESC compared to DMSO (DM) control and XS treatment. (F) Similarly, HLC showed significant difference in mean LDLR mRNA with treatment and within cell type; in both C and H1 cells, means were different in response to RS treatment in comparison to DM and XS treatment, although no difference was detected within the NC cell treatment groups. The graph values represent the mean±s.d. (n=3) per treatment, per cell type of three experiments repeated in the laboratory using a two-way ANOVA Holm–Sidak post-hoc test. **P<0.01, ***P<0.001, ****P<0.0001, #P<0.05 between RS-treated cell types.