Induction of EGFR tyrosine kinase in the gastric mucosa of diabetic rats.
Diabetes mellitus is associated with spontaneous gastric mucosal injury and enhanced susceptibility of the mucosa to damaging agents. Little information is available about the biochemical changes that occur in the gastric mucosa of diabetes mellitus. Evidence is accumulating that tyrosine kinases, particularly the EGF-receptor (EGFR), are involved in regulating a variety of structural and functional properties of the gastric mucosa. The primary objectives of this investigation were to determine whether diabetes induces morphological changes in the gastric mucosa, and if so, whether these changes are associated with alterations in EGFR tyrosine kinase. Diabetes-induced changes in gastric mucosal morphology were also examined. Diabetes was induced in 3- to 4-month-old male Fischer-344 rats by streptozotocin (STZ; 45 mg/kg; i.v.). Four weeks after induction of diabetes mellitus, the gastric mucosa of overnight-fasted rats was found to be slightly atrophic. A reduction in gastric mucosal thickness with deposition of fibrous tissue above the muscularis layer was observed in the stomach of overnight-fasted diabetic rats. These changes were associated with a marked stimulation in tyrosine kinase activity and protein expression of EGFR. The relative concentrations of several precursor forms of TGF-alpha in both membrane and cytosolic fractions from the gastric mucosa of overnight-fasted diabetic rats were also found to be significantly above the corresponding controls. This suggests that endogenous TGF-alpha may play a critical role in regulating mucosal EGFR tyrosine kinase through a juxtacrine/paracrine mechanism.
Khan
A J
AJ
Department of Internal Medicine, Detroit, Michigan 48201, USA.
Fligiel
S E
SE
Liu
L
L
Jaszewski
R
R
Chandok
A
A
Majumdar
A P
AP
D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases