Unraveling the Connection Between Ion Channels and Pancreatic Stellate Cell Activation.

Abstract

Quiescent pancreatic stellate cells (PSCs) represent only a very low proportion of the pancreatic tissue, but their activation leads to stroma remodeling and fibrosis associated with pathologies such as chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC). PSC activation can be induced by various stresses, including acidosis, growth factors (PDGF, TGFβ), hypoxia, high pressure, or intercellular communication with pancreatic cancer cells. Activated PSC targeting represents a promising therapeutic strategy, but little is known regarding the molecular mechanisms underlying the activation of PSCs. Identification of new biomarkers of PSC activation associated with desmoplasia in chronic pancreatitis and PDAC could lead to new therapeutic targets for exocrine pancreatic disease treatments. Ion channels and transporters are transmembrane proteins involved in numerous physiological and pathological processes, including PDAC. They are well known to act as biosensors of the tissue microenvironment, and they can be easily accessible for drugs. However, their role in PSC activation is not fully understood. In this review, we briefly discuss the role of activated PSCs in pancreas inflammation and pathological fibrosis (associated with chronic pancreatitis and PDAC), and we describe the role of specific ion channels and transporters (Ca²⁺, K⁺, Na⁺ and Cl^-) in these processes in the light of recent literature.