Helicobacter pylori-induced changes in microtubule dynamics conferred by α-tubulin phosphorylation on Ser/Tyr mediate gastric mucosal secretion of matrix metalloproteinase-9 (MMP-9) and its modulation by ghrelin.
Regulation of matrix metalloproteinase-9 (MMP-9) secretion in response to proinflammatory challenge remains under a strict control of factors that affect the stability dynamics of the major cytoskeleton polymeric structures, microtubules (MTs). In this study, we report that H. pylori LPS-elicited induction gastric mucosal MMP-9 secretion is accompanied by the enhancement in MT stabilization as evidenced by the increase in α-tubulin acetylation and detyrosination while the modulatory influence of hormone, ghrelin, is associated with MT destabilization and reflected in a decrease in α-tubulin acetylation and detyrosination. Further, we reveal that the LPS-induced enhancement in MT stabilization and up-regulation in MMP-9 secretion as well as the modulatory influence of ghrelin occur with the involvement of PKCδ and SFK. The LPS effect is reflected in a marked increase in PKCδ-mediated α-tubulin phosphorylation on Ser, while the modulatory effect of ghrelin on MT dynamics and MMP-9 secretion is manifested by the SFK-dependent phosphorylation of α-tubulin on Tyr. Moreover, the changes in α-tubulin phosphorylation and MT stabilization dynamics occur in concert with the Golgi recruitment and activation of PKD2 and Arf-GEF. The findings demonstrate that the enhancement in gastric mucosal MMP-9 secretion in response to H. pylori and its modulation by ghrelin are the result of changes in MT dynamics conferred by PKCδ/SFK- mediated α-tubulin Ser/Tyr phosphorylation.
Research Center, C875 Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ, 07103-2400, USA. slomiabr@sdm.rutgers.edu.
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Slomiany
Research Center, C875 Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ, 07103-2400, USA.
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Slomiany
D000818:Animals; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D054439:Ghrelin / Q000494:pharmacology*; D016480:Helicobacter pylori; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012694:Serine / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D054439:Ghrelin; D014404:Tubulin; D014443:Tyrosine; D012694:Serine; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
Gastric mucosa; Ghrelin; H. pylori LPS; MMP-9; MT stabilization; α-tubulin Tyr/Ser phosphorylation