Pathogenic Role of mTORC1 and mTORC2 in Pulmonary Hypertension
Haiyang Tang, Kang Wu, Jian Wang, Sujana Vinjamuri, Yali Gu, Shanshan Song, Ziyi Wang, Qian Zhang, Angela Balistrieri, Ramon J. Ayon, Franz Rischard, Rebecca Vanderpool, Jiwang Chen, Guofei Zhou, Ankit A. Desai, Stephen M. Black, Joe G.N. Garcia, Jason X.-J. Yuan and Ayako Makino
Rictor (mTORC2) Contributes to Regulating PDGFR Expression in Smooth Muscle Cells
SM-specific conditional and inducible KO of Rictor up-regulates the protein expression of platelet-derived growth factor receptors (PDGFRs) in isolated PA. (A) Western blot analyses on PDGFRα and PDGFRβ, as well as phosphorylated AKT at S473 and T308, in PA isolated from WT and RictorSM−/− mice (a). Summarized data (mean ± SE; n = 3 in each group) showing PA expression levels of PDGFRα, PDGFRβ, pAKT (S473), and pAKT (T308) in WT and RictorSM−/− mice in PA isolated from WT and RictorSM−/− mice (b). p values, determined by Student's t-test are indicated in b, WT vs. RictorSM−/− mice. (B) Western blot analyses on PDGFRα, PDGFRβ, pAKT (S473), and AKT in PA isolated from normoxic and chronically hypoxic WT and RictorSM−/− mice (a). Summarized data (mean ± SE, n = 3 in each group) showing PA expression levels of PDGFRα, PDGFRβ, and pAKT (S473) in WT and RictorSM−/− mice under normoxic and hypoxic conditions (b). Kruskal-Wallis test, p = 0.02 and Dunn test, *p < 0.05 versus Normoxia-WT or Normoxia-RictorSM−/−. (C) Summarized data (mean ± SE; n = 3 in each group) showing the changes (or differences) in PA expression levels of PDGFRα (left panel) and PDGFRβ (right panel) in RictorSM−/− mice (compared with the WT controls) during normoxia and hypoxia. (D) Summarized data (mean ± SE; n = 3 in each group) showing the hypoxia-induced changes in the protein expression level of PDGFRα and PDGFRβ in WT mice and RictorSM−/− mice. The numbers of experiments (n) for each group are also indicated in each bar. Abbreviations as in Figure 1.