The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP/regI and PAP/regIII

Abstract

IntroductionIn patients with infection and sepsis serum levels of Pancreatic Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP during these conditions is presumably the pancreas, however, an intestinal origin cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was identified in the pancreas. These proteins were also localized in intestinal organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal models of sepsis and in healthy humans.ResultsPSP and PAP responded to remote lesions in rats although the pancreatic response was much more pronounced than the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content in the pancreas compared to any other organ while PAP was most abundant in the small intestine. Both proteins responded to CLP or sham operation in the pancreas. PSP also increased in the intestine during CLP. The distribution of PSP and PAP in human tissue mirrored the distribution in the murine models.Materials and methodsDistribution of PSP and PAP was visualized by immunohistochemistry. Rats and mice underwent midline laparotomies followed by mobilization of tissue and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture (CLP) procedures or sham laparotomies were performed. Human tissue extracts were analyzed for PSP and PAP.ConclusionsThe pancreas reacts to remote lesions and septic insults in mice and rats with increased PSP synthesis, while PAP is selectively responsive to septic events. Furthermore, our results suggest that serum PSP in septic patients is predominantly derived through an acute phase response of the pancreas.

Identification of regenerating island-derived protein 3E in dogs

“…Analysis of RNA-Seq data derived from Barkbase ( 32 ) revealed marked differences in expression of REG3E RNA between tissues, with the highest number of reads found in the pancreas, followed by the cardiac atrium and the small intestine. In humans and rodents, REG1A protein is predominantly produced in the pancreas, whereas REG3A is primarily found in the small intestine ( 35 ). This is paralleled by findings in lambs, where a “PAP-like protein” mRNA was expressed 300-fold higher in ileal and jejunal Peyer's patches compared to the pancreas ( 30 ).…”

“…Recombinant human REG1A and REG3A proteins, produced in Pichia pastoris culture, and antibodies raised in rabbits and guinea pigs against human recombinant REG1A and REG3A as previously described ( 6 , 34 , 35 ) were obtained from the Pancreas Research Laboratory, University of Zürich, Switzerland.…”

“…Immunohistochemistry was performed at the Pancreas Research Laboratory of the University of Zürich, using a previously established protocol ( 35 , 36 ). Briefly, sections of formalin-fixed, paraffin-embedded pancreatic tissue were deparaffinised, boiled in citrate for antigen demasking, and blocked prior to incubation with the primary antibody directed against human REG1A or REG3A, respectively, at a 1:800 dilution.…”

Measurement of Pancreatic Stone Protein in the Identification and Management of Sepsis

“…This observation was then clinically confirmed in a cohort of trauma patients, in which serum PSP rises early after trauma for those patients that later develop infection and sepsis [29]. Reding et al further showed that the pancreas senses remote organ damage and systemic stress and responds by secreting PSP, particularly when associated with septic complications [30].…”

Pancreatic Stone Protein: Review of a New Biomarker in Sepsis

“…This observation was then clinically confirmed by the demonstration in humans that the pancreas senses remote organ damage and systemic stress and responds by secreting PSP in the absence of pancreatic tissue damage [34]. As an acute-phase protein, PSP might be involved in promoting cell proliferation during regenerative processes [35], through regulation by IL-6 and other cytokines that are released after tissue injury [36,37], rendering to the pancreas what Reding et al [38] call "the role of an acute phase organ".…”