Type 2 diabetes mellitus stimulated pulmonary vascular inflammation and exosome biogenesis in rats.
Jafar RezaieHossein HosseinpourReza RahbarghaziRana KeyhanmaneshShokoufeh KhanzadehMahdi MahdipourJafar SoleimanpourMahdi AhmadiPublished in: Cell biochemistry and function (2022)
It has been shown that type 2 Diabetes Mellitus (T2DM) changes the paracrine activity of several cell types. Whether the biogenesis of exosomes is changed during diabetic conditions is the subject of debate. Here, we investigated the effect of T2M on exosome biogenesis in rat pulmonary tissue. Rats received a high-fat diet regime and a single low dose of Streptozocin to mimic the T2DM-like condition. A total of 8 weeks after induction of T2DM, rats were subjected to several analyses. Besides histological examination, vascular cell adhesion molecule 1 (VCAM-1) levels were detected using immunohistochemistry (IHC) staining. Transcription of several genes such as IL-1β, Alix, and Rab27b was calculated by real-time polymerase chain reaction assay. Using western blot analysis, intracellular CD63 levels were measured. The morphology and exosome secretion activity were assessed using acetylcholinesterase (AChE) assay and scanning electron microscopy, respectively. Histological results exhibited a moderate-to-high rate of interstitial pneumonia with emphysematous changes. IHC staining showed an increased VCAM-1 expression in the diabetic lungs compared with the normal conditions (p < .05). Likewise, we found the induction of IL-1β, and exosome-related genes Alix and Rab27b under diabetic conditions compared with the control group (p < .05). Along with these changes, protein levels of CD63 and AChE activity were induced upon the initiation of T2DM, indicating accelerated exosome biogenesis. Taken together, current data indicated the induction of exosome biogenesis in rat pulmonary tissue affected by T2DM. It seems that the induction of inflammatory niche is touted as a stimulatory factor to accelerate exosome secretion.
Keyphrases
- high fat diet
- glycemic control
- cell adhesion
- type diabetes
- oxidative stress
- low dose
- electron microscopy
- pulmonary hypertension
- insulin resistance
- adipose tissue
- mesenchymal stem cells
- high throughput
- stem cells
- wound healing
- single cell
- poor prognosis
- transcription factor
- metabolic syndrome
- south africa
- high dose
- gene expression
- high resolution
- electronic health record
- genome wide
- diabetic rats
- small molecule
- cell therapy
- dna methylation
- acute respiratory distress syndrome
- flow cytometry
- endothelial cells
- mass spectrometry
- protein protein
- nk cells
- cardiovascular risk factors
- high speed
- atomic force microscopy
- finite element