Fig. 4: CH induces dissociation of FKBP12.6 from RyR2 and the effect of PH. | Nature Communications

Fig. 4: CH induces dissociation of FKBP12.6 from RyR2 and the effect of PH.

From: Rieske iron-sulfur protein induces FKBP12.6/RyR2 complex remodeling and subsequent pulmonary hypertension through NF-κB/cyclin D1 pathway

Fig. 4

a Representative Co-IP and western blot of RyR2 and FKBP12.6 from CH induced PH. FKBP12.6 is immunoprecipitated with an anti-RyR2 antibody and then immunoblotted with anti-FKBP12.6 antibody. Tissue is taken from Nor and CH mice’s pulmonary arteries (PA) and mesentery arteries (MA) (n = 3 independent studies, 5 mice per study). Bar graph summarizes the effect of CH on the association ratio of FKBP12.6 to RyR2. b Representative Co-IP and western blot of RyR2/FKBP12.6 complex from patients with PH and age-matched non-PH (Con) human PAs. Bar graph depicts the association ratio of FKBP12.6 to RyR2 (n = 3 independent studies). c Representative pictures of FRET measurement between donor (FKBP12.6) and acceptor (RyR2) in PASMC. At different levels of acceptor, WT Nor PASMC (black spot) transferred more energy than CH PASMC (red spot), which indicates the experiment is independent of acceptor. Bar graph summarizes average percentage of FRET efficiencies between RyR2/FKBP12.6 pairs in Nor and CH PASMC (n = 5 independent studies). d In vivo PASMC proliferation (Ki-67 staining) after 3 weeks CH in FKBP12.6−/− mice (n = 5 independent studies, 50 vessels per study). e Summarized the effect of CH on the RVSP in WT and FKBP12.6−/− PH mice model. Ratio of RV/LV + S to measure RV hypertrophy (n = 7 independent studies, 5 mice per study). f Representative Co-IP and western blot of RyR2/FKBP12.6 association from low dosage and high dosage FK506 treatment groups. Bar graphs describe the summarized results of FKBP12.6/RyR2 binding ratio in FK506 treating PH model (n = 4 independent studies, 5 mice per studies). g In vivo pulmonary vascular remodeling evaluated by proportion of non-(Non), partially (Par), or fully (Mus) muscularized PAs and medial wall thickness (n = 7 independent studies, 60 vessels per study). h Impact of 3-weeks low dosage FK506 (0.05 mg/kg/d) and high dosage FK506 (1 mg/kg/d) on RVSAP and RV/LV + S, indicating low dosage FK506 has protective effect however high dosage FK506 facilitates the development of PH (n = 7 independent studies, 5 mice per study). Data are expressed as mean ± standard error. (*P < 0.05, using one-way ANOVA test or Student’s t test).

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