Aref Delkhosh; Rahim Hobbenaghi; Reza Rahbarghazi; Mahdi Ahmadi; Jafar Rezaie
Volume 13, Issue 4 , December 2022, , Pages 489-493
Abstract
Diabetes mellitus is one of the leading causes of death globally. The development of cellular injuries and impaired energy metabolism are involved in the pathogenesis of diabetes mellitus, leading to severe diabetic complications in different tissues such as the pulmonary tissue. Autophagy is a double-edged ...
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Diabetes mellitus is one of the leading causes of death globally. The development of cellular injuries and impaired energy metabolism are involved in the pathogenesis of diabetes mellitus, leading to severe diabetic complications in different tissues such as the pulmonary tissue. Autophagy is a double-edged sword mechanism required for maintaining cell survival and homeostasis. Any abnormalities in autophagic response can lead to the progression of several diseases. Here, we aimed to assess the effect of diabetic conditions on the autophagic response and exosome secretion in a rat model of type 2 diabetes mellitus. The experimental diabetic group received 45.00 mg kg-1 streptozocin (STZ) dissolved in 0.10 M sodium citrate. After 4 weeks, we monitored autophagic response and exosome biogenesis in the pulmonary tract using immunohistochemistry (IHC) and Real-time polymerase chain reaction analyses, respectively. Histological examination revealed the interstitial bronchopneumonia indicating enhanced immune cell infiltration into the pulmonary parenchyma. Immunohistochemistry staining displayed an enhanced autophagic response through the induction of microtuble-associated protein light chain 3 (LC3) and protein sequestosome 1 (P62) compared to the control rats. These changes coincided with significant induction of tetraspanin CD63 in STZ-induced diabetic rats relative to control rats. In conclusion, a diabetic condition can increase the autophagic response in pulmonary tissue. The accumulation of P62 in the pulmonary niche exhibits an incomplete autophagic response. The abnormal autophagy response can increase pulmonary cell sensitivity against injuries.
Aram Mokarizadeh; Nowruz Delirezh; Ahhmad Morshedi; Ghasem Mosayebi; Bahram Dalir-Naghadeh
Volume 3, Issue 4 , December 2012, , Pages 257-261
Abstract
Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory ...
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Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory molecules onto auto-reactive cells through exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells. The exosomes were isolated from supernatant of mesenchymal stem cells culture. Resultant exosomes co-cultured with lymphocytes were harvested from established EAE mice in the presence of antigenic MOG35-55 peptide. After 24 hr, insertion of exosomal tolerogenic molecules (PD-L1, TGF-β, galectin-1) onto auto-reactive cells were explored through flow cytometry. The potency of exosomal inserted membrane molecules to modulate phenotype of auto-reactive lymphocytes was assessed upon ELISA test for their-derived cytokines IFN-γ and IL-17. Incorporation of exosomal molecules into lymohocytes’ membrane was confirmed by flow cytometric analyses for surface levels of mentioned molecules. Additionally, the decreased secretion of IFN-γ and IL-17 were detected in exosome pre-treated lymphocytes upon stimulation with MOG peptide. Mesenchymal stem cells -derived exosomes showed to be efficient organelles for insertion of bioactive tolerogenic molecules onto auto-reactive cells and modulation of their phenotypes.
