Previous studies have demonstrated that hypoxia can induce phenotypic modulation of pulmonary smooth muscle cells; however, the mechanisms remain unclear. The present study aimed to investigate the effect of the GTPase Rab6A-mediated phenotypic modulation and other activities of rat pulmonary artery smooth muscle cells (RPASMCs). We revealed that Rab6A was induced by hypoxia (1% O ) and was involved in a hypoxia-induced phenotypic switch and endoplasmic reticulum stress (ERS) in RPASMCs. After 48 hours of hypoxia, the expression of the phenotype marker protein smooth muscle actin was downregulated and vimentin (VIM) expression was upregulated. Rab6A was upregulated after 48 hours of hypoxia, and the level of glucose-regulated protein, 78 kDa (GRP78) after 12 hours of hypoxic stimulation was also increased. After transfection with a Rab6A short interfering RNA under hypoxic conditions, the expression levels of GRP78 and VIM in RPASMCs were downregulated. Overall, hypoxia-induced RPASMCs to undergo ERS followed by phenotypic transformation. Rab6A is involved in this hypoxia-induced phenotypic modulation and ERS in RPASMCs.
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http://dx.doi.org/10.1002/jcb.28060 | DOI Listing |
Nat Commun
January 2025
Laboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany.
The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its DNA end protection activity during class switch recombination. In this study, we showed that RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into plasma cells upon immunization.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Internal Medicine I, Ulm University Hospital, Ulm, Germany
Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.
View Article and Find Full Text PDFHorm Behav
January 2025
Department of Integrative Biology, University of Texas at Austin, Austin, TX 78712, United States of America. Electronic address:
Individual variation in stress coping styles is widespread and consequential to health and fitness. Proactive (bold behavior, low stress reactivity, low cognitive flexibility) and reactive (shy behavior, high stress reactivity, high cognitive flexibility) coping styles are found in many species, but the developmental forces shaping them remain elusive. We examined how social influences, specifically mating interactions, shape the development of adult female coping styles with a manipulative rearing experiment using El Abra swordtails, Xiphophorus nigrensis.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, China. Electronic address:
Exosomes, which are small extracellular vesicles (sEVs), serve as versatile regulators of intercellular communication in the progression of various diseases, including neurological disorders. Among the diverse array of cargo they carry, non-coding RNAs (ncRNAs) play key regulatory roles in various pathophysiological processes. Exosomal ncRNAs derived from distinct cells modulate their reciprocal crosstalk locally or remotely, thereby mediating neurological diseases.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, 138 Xianlin Rd., Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Rd., Nanjing 210023, China. Electronic address:
Neuroinflammation mediated by microglia is considered the primary cause and pathological process of anxiety. Abnormal glycolysis of microglia is observed during microglia activation. However, whether regulating the Warburg effect in microglia can effectively intervene anxiety and its potential mechanisms have not been elucidated.
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