Establishment of culture systems of human gastric epithelium for the study of pepsinogen and gastric lipase synthesis and secretion.
A main purpose of gastric secretion pertains to the digestion of dietary proteins and involves the release of pepsinogens by the fundic and antral mucosa. Over the last decade, data on human gastric physiology has expanded to equally include a significant role in fat digestion. Characteristics of human gastric lipase (HGL) such as optimum acid pH, resistance to proteolysis and non requirement of bile salts or cofactors, are advantageous in gastric lipolysis. Furthermore, the importance of HGL increases in the context of perinatal physiology and pathological situations where secretion of HGL could compensate, to some extent the depressed pancreatic activities. It is therefore important to understand the regulatory mechanisms involved in the synthesis and secretion of human gastric digestive enzymes. The establishment of an organ culture technique as well as a novel primary culture system of human gastric epithelium permitted us to demonstrate that Pg5 and HGL are colocalized in human chief cells and both digestive enzymes are efficiently synthesized and secreted in explants and primary cultures. Pepsin activity rises at the cellular level while its secretion remains constant. In contrast, cellular lipase activity drastically diminishes while being preferentially secreted. This nonparallelism supports the concept that Pg5 and HGL are differently regulated in culture. Furthermore, EGF downregulates HGL expression at the mRNA level via the p42/44(MAPK) pathway without affecting Pg5. Future studies should be designed to fully understand the cellular and molecular mechanisms involved in regulating HGL activity in normal and pathological conditions.
Basque
J R
JR
MRC Research Group on Functional Development and Physiopathology of the Gastrointestinal Tract, Department of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke (Québec) Canada.
Ménard
D
D
D018929:Cell Culture Techniques / Q000379:methods; D016895:Culture Media, Serum-Free; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D005333:Fetus; D005753:Gastric Mucosa / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000096:biosynthesis* / Q000378:metabolism; D009924:Organ Culture Techniques / Q000379:methods; D020116:Pepsinogen A / Q000096:biosynthesis* / Q000378:metabolism
D016895:Culture Media, Serum-Free; D020116:Pepsinogen A; D008049:Lipase