title: Inactivated Pseudomonas aeruginosa inhibits hypoxia-induced pulmonary hypertension by preventing TGF-β1/Smad signaling.
abstract: Pseudomonas aeruginosa is one of the common colonizing bacteria of the human body and is an opportunistic pathogen frequently associated with respiratory infections. Inactivated P. aeruginosa (IPA) have a variety of biological effects against inflammation and allergy. Transforming growth factor-β (TGF-β) signaling plays a critical role in the regulation of cell growth, differentiation, and development in a wide range of biological systems. The present study was designed to investigate the effects of IPA on TGF-β/Smad signaling in vivo, using a hypoxia-induced pulmonary hypertension (PH) rat model. Sprague Dawley rats (n=40) were exposed to 10% oxygen for 21 days to induce PH. At the same time, IPA was administered intravenously from day 1 to day 14. Mean pulmonary artery pressure (mPAP) and the right ventricle (RV) to left ventricle plus the interventricular septum (LV+S) mass ratio were used to evaluate the development of PH. Vessel thickness and density were measured using immunohistochemistry. Primary arterial smooth muscle cells (PASMCs) were isolated and the proliferation of PASMCs was assayed by flow cytometry. The production of TGF-β1 in cultured supernatant of PASMCs was assayed by ELISA. The expression levels of α-smooth muscle actin (α-SMA), TGF-β1 and phospho-Smad 2/3 in PASMCs were assayed by western blot. Our data indicated that IPA attenuated PH, RV hypertrophy and pulmonary vascular remodeling in rats, which was probably mediated by restraining the hypoxia-induced overactive TGF-β1/Smad signaling. In conclusion, IPA is a promising protective treatment in PH due to the inhibiting effects on TGF-β1/Smad 2/3 signaling.
authors: Department of Cardiac Surgery, Liaocheng People's Hospital, Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China.
authors: S D
authors: SD
authors: Chai
authors: Department of Cardiac Surgery, Liaocheng People's Hospital, Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China.
authors: T
authors: T
authors: Liu
authors: Department of Cardiac Surgery, Liaocheng People's Hospital, Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China.
authors: M F
authors: MF
authors: Dong
authors: Department of Cardiac Surgery, Liaocheng People's Hospital, Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China.
authors: Z K
authors: ZK
authors: Li
authors: Department of Cardiac Surgery, Liaocheng People's Hospital, Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China.
authors: P Z
authors: PZ
authors: Tang
authors: Department of Cardiac Surgery, Liaocheng People's Hospital, Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China.
authors: J T
authors: JT
authors: Wang
authors: Department of Cardiac Surgery, Liaocheng People's Hospital, Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China.
authors: S J
authors: SJ
authors: Ma
mesh_terms: D000199:Actins / Q000032:analysis / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000032:analysis / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000378:metabolism*
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse