A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Pancreas Whole Tissue Transcriptomics Highlights the Role of the Exocrine Pancreas in Patients With Recently Diagnosed Type 1 Diabetes
Tekijät: Välikangas Tommi, Lietzén Niina, Jaakkola Maria K, Krogvold Lars, Eike Morten C, Kallionpää Henna, Tuomela Soile, Mathews Clayton, Gerling Ivan C, Oikarinen Sami, Hyöty Heikki, Dahl-Jorgensen Knut, Elo Laura L, Lahesmaa Riitta
Kustantaja: Frontiers Media S.A.
Julkaisuvuosi: 2022
Journal: Frontiers in Endocrinology
Tietokannassa oleva lehden nimi: Frontiers in Endocrinology
Vuosikerta: 13
eISSN: 1664-2392
DOI: https://doi.org/10.3389/fendo.2022.861985
Verkko-osoite: https://doi.org/10.3389/fendo.2022.861985
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/175288922
Although type 1 diabetes (T1D) is primarily a disease of the pancreatic beta-cells, understanding of the disease-associated alterations in the whole pancreas could be important for the improved treatment or the prevention of the disease. We have characterized the whole-pancreas gene expression of patients with recently diagnosed T1D from the Diabetes Virus Detection (DiViD) study and non-diabetic controls. Furthermore, another parallel dataset of the whole pancreas and an additional dataset from the laser-captured pancreatic islets of the DiViD patients and non-diabetic organ donors were analyzed together with the original dataset to confirm the results and to get further insights into the potential disease-associated differences between the exocrine and the endocrine pancreas. First, higher expression of the core acinar cell genes, encoding for digestive enzymes, was detected in the whole pancreas of the DiViD patients when compared to non-diabetic controls. Second, In the pancreatic islets, upregulation of immune and inflammation related genes was observed in the DiViD patients when compared to non-diabetic controls, in line with earlier publications, while an opposite trend was observed for several immune and inflammation related genes at the whole pancreas tissue level. Third, strong downregulation of the regenerating gene family (REG) genes, linked to pancreatic islet growth and regeneration, was observed in the exocrine acinar cell dominated whole-pancreas data of the DiViD patients when compared with the non-diabetic controls. Fourth, analysis of unique features in the transcriptomes of each DiViD patient compared with the other DiViD patients, revealed elevated expression of central antiviral immune response genes in the whole-pancreas samples, but not in the pancreatic islets, of one DiViD patient. This difference in the extent of antiviral gene expression suggests different statuses of infection in the pancreas at the time of sampling between the DiViD patients, who were all enterovirus VP1+ in the islets by immunohistochemistry based on earlier studies. The observed features, indicating differences in the function, status and interplay between the exocrine and the endocrine pancreas of recent onset T1D patients, highlight the importance of studying both compartments for better understanding of the molecular mechanisms of T1D.
Ladattava julkaisu This is an electronic reprint of the original article. |