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. 2020 Jul 15;11:3527. doi: 10.1038/s41467-020-17314-1

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — a A representative western blot of p65/p50 translocation from cytoplasm (Cyto) to nuclei (Nu) in RyR2KO mice. b Bar graphs depict the expression of p65/p50 in cytoplasm normalized by GAPDH (n = 3 independent studies, 5 mice per study). c Summarized data of the expression of p65/p50 in nuclei normalized by Lamin A (n = 3 independent studies, 5 mice per study). d A representative western blot of p65/p50 translocation from cytoplasm (Cyto) to nuclei (Nu) in S107 treating group. Bar graphs depict the expression of p65/p50 in cytoplasm and nuclei in S107 treatment group. The protein levels are normalized by GAPDH and Lamin A respectively (n = 3 independent studies, 5 mice per study). e A representative western blot of cyclin D1 and IκB expression in RyR2KO and S107 treatment groups. e IκB and f cyclin D1 expression normalized by GAPDH (n = 3 independent studies, 5 mice per study). g Western blot shows that PDTC inhibits the over-activation of cyclin D1 in PH model (n = 3 independent studies, 5 mice per study). h PASMC resting [Ca²⁺]_i in either Nor or CH is not changed in PDTC (100 mg/kg/d) treatment group (n = 5 independent studies, 80 cells per study). i Pre-incubation with PDTC (0.1 mM) does not change the contractility of PAs (n = 6 independent studies, 5 PA stripes per study). j Typical lung sections of pulmonary arteries (bar scale: 50 µm). In vivo evaluation of pulmonary vascular remodeling by measuring proportion of non-(Non), partially (Par), or fully (Mus) muscularized PAs (n = 7 independent studies, 60 vessels per study). k PASMC proliferation (Ki-67 staining) in vivo in PH models and medial wall thickness of PAs. (n = 7 independent studies, 60 vessels per study). l Application of PDTC suppresses the elevation of RVSP and RV hypertrophy in PH model (n = 5 independent studies, 5 mice per study) without major effect of RyR2 KO mice. m Schematic illustration summarizes the proposed model of RISP/ROS-RyR2/FKBP12.6-NF-κB/cyclin D1 pathway. Data are expressed as mean ± standard error. (*P < 0.05, using one-way ANOVA test).