Epidermal growth factor and transforming growth factor alpha down-regulate human gastric lipase gene expression.
OBJECTIVE
It was recently reported that human gastric lipase (HGL) activity is modulated by epidermal growth factor (EGF). The aims of this study were to establish the cellular localization of HGL, to assess the correlation between HGL messenger RNA (mRNA) and protein levels, and to establish the molecular mechanism of action of EGF and its homologue transforming growth factor alpha (TGF-alpha) on HGL expression.


METHODS
Cellular localization of HGL was determined by immunohistochemistry using a polyclonal antibody. Enzymic determinations, Western blotting, and Northern hybridization were used to analyze expression of HGL mRNA, protein, lipase activity, and the p42/p44(mapk) activation status.


RESULTS
HGL was localized in the secretory granules of gastric chief cells as early as 13 weeks. A close parallelism was found between the variations of mRNA, protein, and enzymic activity. EGF and/or TGF-alpha down-regulated HGL mRNA levels and decreased enzymic activity. The role of the mitogen-activated protein kinase cascade in the regulation of HGL expression was highlighted by the use of MAP kinase kinase-1/2 inhibitor PD98059, which blunted both the activation of p42/p44(mapk) and the down-regulation of HGL mRNA induced by EGF and/or TGF-alpha.


CONCLUSIONS
The expression of HGL is regulated at the mRNA level, and the down-regulatory action of EGF and/or TGF-alpha on HGL involves the stimulation of p42/p44(mapk) cascade.
Tremblay
E
E
Groupe du Conseil de Recherches Médicales sur le Développement Fonctionnel et la Physiopathologie du Tube Digestif, Département d'Anatomie et de Biologie Cellulaire, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Basque
J R
JR
Rivard
N
N
Ménard
D
D
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D008049:Lipase / Q000235:genetics*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D013270:Stomach / Q000201:enzymology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D008049:Lipase