2. Academic Validation
  3. Endothelial Cells Promote Pseudo-islet Function Through BTC-EGFR-JAK/STAT Signaling Pathways

Endothelial Cells Promote Pseudo-islet Function Through BTC-EGFR-JAK/STAT Signaling Pathways

  • Ann Biomed Eng. 2024 Jun 3. doi: 10.1007/s10439-024-03548-3.
Lin Wang # 1,  Jian Wan # 1 2,  Yang Xu # 1,  Yan Huang 1 2,  Dongzhi Wang 1 2,  Donghui Zhu 1,  Qiyang Chen 1,  Yuhua Lu 3 4,  Qingsong Guo 5 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
  • 2 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
  • 3 Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China. lyh76@126.com.
  • 4 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. lyh76@126.com.
  • 5 Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China. ntgglj@163.com.
  • 6 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. ntgglj@163.com.
  • # Contributed equally.
PMID: 38829457 DOI: 10.1007/s10439-024-03548-3
Abstract

Interactions between cells are of fundamental importance in affecting cell function. In vivo, endothelial cells and islet cells are close to each other, which makes endothelial cells essential for islet cell development and maintenance of islet cell function. We used endothelial cells to construct 3D pseudo-islets, which demonstrated better glucose regulation and greater Insulin secretion compared to conventional pseudo-islets in both in vivo and in vitro trials. However, the underlying mechanism of how endothelial cells promote beta cell function localized within islets is still unknown. We performed transcriptomic Sequencing, differential gene analysis, and enrichment analysis on two types of pseudo-islets to show that endothelial cells can promote the function of internal beta cells in pseudo-islets through the BTC-EGFR-JAK/STAT signaling pathway. Min6 cells secreted additional BTC after co-culture of endothelial cells with MIN6 cells outside the body. After BTC knockout in vitro, we found that beta cells functioned differently: Insulin secretion levels decreased significantly, while the expression of key proteins in the EGFR-mediated JAK/STAT signaling pathway simultaneously decreased, further confirming our results. Through our experiments, we elucidate the molecular mechanisms by which endothelial cells maintain islet function in vitro, which provides a theoretical basis for the construction of pseudo-islets and islet cell transplants for the treatment of diabetes mellitus.

Keywords

BTC; Endothelial cells; JAK-STAT signaling pathways; MIN6 cells; Pseudo-islet.

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