Molecular and cellular regulation of pancreatic acinar cell function - PubMed (original) (raw)

Review

Molecular and cellular regulation of pancreatic acinar cell function

Sohail Husain et al. Curr Opin Gastroenterol. 2009 Sep.

Abstract

Purpose of review: This review focuses on studies from the past year that have greatly advanced our understanding of molecular and cellular regulation of pancreatic acinar cell function.

Recent findings: Recent advances focus on signals dictating pancreatic development, acinar cell fate, pancreatic growth, and secretion. Regeneration of acinar cells after pancreatitis depends on expression of embryonic signals in mature acinar cells. In this setting, acinar cells can also transdifferentiate into adipose cells. With the forced induction of certain early and endocrine-driving transcription factors, acinar cells can also transdifferentiate into beta-cells. There has also been an increased understanding of acinar-to-ductal metaplasia and the subsequent formation of pancreatic intraepithelial neoplasia lesions. Multiple proteins involved in secretion have been characterized, including small guanosine triphosphate-binding proteins, soluble N-ethylmaleimide-sensitive factor attachment proteins, and ion channels.

Summary: These findings demonstrate the regenerative potential of the acinar cell to mitigate injurious states such as pancreatitis. The ability of acinar cells to transdifferentiate into beta-cells could potentially provide a treatment for diabetes. Finally, the results might be helpful in preventing malignant transformation events arising from the acinar cell. Developments in proteomics and computer modeling could expand our view of proteins mediating acinar cell function.

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Figures

Figure 1

Figure 1. Developmental and differentiation patterns relating to the pancreatic acinar cell

(a) Foregut endoderm gives rise to pancreatic progenitors that then differentiate into acinar, duct, or islet cells. (b) In response to pancreatic injury, acinar cells can regenerate by dedifferentiating to a ductal epithelium and then redifferentiating to mature acinar cells (solid arrows). They can transdifferentiate to adipocytes or β-cells, depending on genetic and environmental cues (dashed arrows). However, the dedifferentiated state is prone to neoplastic transformation, such as to a PanIN lesion. PanIN, pancreatic intraepithelial neoplasia.

Figure 2

Figure 2. Zymogen granule proteins

A quantitative proteomics approach has detected previously known zymogen granule proteins (myosin V, VAMPs, syntaxins, Rab proteins and SCAMP) as well as identified new ones (Tm63A and presenilin 2). Luminal proteins include digestive enzymes as well as matrix proteins (GP2, GP3, syncollin, and ZG16). Recent advances describing the functions of some of these proteins are discussed in the text. KCNQ1, potassium voltage-gated channel, KQT-like subfamily, member 1; SCAMP, secretory carrier membrane protein; SNAP, synapse-associated protein; VAMP, vesicle-associated membrane protein.

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