Determination of molecular mechanisms of cellular plasticity and pancreatic tissue remodeling under conditions of dosed exogenous hypoxia
DOI:
https://doi.org/10.14739/2409-2932.2026.1.351389Keywords:
Wistar rats, pancreas, genes, dosed exogenous hypoxia, endocrine cells, cellular plasticity, tissue remodelingAbstract
The endocrine apparatus of the pancreas represents a micro-organ that includes multiple endocrine cell populations that function in close interaction with the microvasculature, extracellular matrix, and immune microenvironment. Within pancreatic islets, oxygen acts not only as an energetic substrate but also as a regulatory signal that modulates transcriptional programs and tissue adaptation through HIF-dependent and HIF-independent mechanisms. Dosed exogenous hypoxia, as a controlled form of intermittent hypoxia, is considered within the concept of hypoxic conditioning and can induce adaptive remodeling, with outcomes critically dependent on the parameters of hypoxic exposure. Investigation of the pancreas under conditions of dosed exogenous hypoxia is therefore promising for delineating the boundary between adaptive reorganization and maladaptive phenotypes and for correlating morphological changes with molecular markers of plasticity and stress responses.
Aim. To determine the molecular mechanisms of cellular plasticity and pancreatic tissue remodeling under conditions of dosed exogenous hypoxia through analysis of the expression profiles of key regulatory genes.
Materials and methods. Gene expression was analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR) with the PARN-405Z RT2 ProfilerTM PCR Array Rat Stem Cell kit (QIAGEN, Germany). The pancreas of experimental animals served as the object of investigation.
Results. Dosed exogenous hypoxia is associated with increased expression of genes belonging to three interconnected functional modules: trophic-cytoprotective, cytoskeletal-secretory, and adhesive-matrix. The most expressed transcriptional changes (Igf1 7.82-fold; Cdc42 4.66-fold; Ncam1 3.34-fold; Col1a1 4.23-fold, 2–ΔΔCt) reflect adaptive remodeling, reinforcement of trophic support, optimization of secretory readiness, and reorganization of islet tissue architecture. Moderate upregulation of Krt15 (2.39-fold) and Cdk1 (2.21-fold) corresponds to activation of reparative-plastic programs without signs of excessive proliferation.
Conclusions. Overall, the transcriptional profile induced by dosed exogenous hypoxia is consistent with controlled adaptive remodeling of the pancreatic endocrine apparatus in response to microenvironmental changes rather than dominance of injury-driven mechanisms.
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