Exploring the role of leucine-rich alpha-2-glycoprotein 1 (LRG1) in the pathophysiology of pancreatic diseases

Abstract

Acute pancreatitis (AP), chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) represent three of the most common disorders affecting the exocrine pancreas. Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a secreted glycoprotein previously implicated in tissue angiogenesis, inflammation, fibrosis and cancer progression. Given that these processes also undergird pancreatic disease development, this study therefore hypothesizes a role of LRG1 in AP, CP and PDAC. LRG1 was shown to be significantly upregulated in the pancreas following caerulein-induced development of AP & CP in mice. Lrg1-deficient mice displayed more severe acinar cell damage and inflammatory response during AP and had exacerbated fibrosis and acinar-ductal metaplasia during CP. Additionally, Lrg1-overexpressing orthotopic tumours generated within wild-type mice were larger in volume compared to their control counterparts, in part due to increased tumour cell proliferation and reduced tumour inflammation and desmoplasia. Taken together, the data provides compelling evidence of the role of LRG1 in the pathophysiology of various pancreatic diseases.