- Gamma-glutamyltransferase of Helicobacter pylori alters the proliferation, migration, and pluripotency of mesenchymal stem cells by affecting metabolism and methylation status
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Zeyu Wang , Weijun Wang , Huiying Shi , Lingjun Meng , Xin Jiang , Suya Pang , Mengke Fan , Rong Lin
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J. Microbiol. 2022;60(6):627-639. Published online April 18, 2022
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DOI: https://doi.org/10.1007/s12275-022-1575-4
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 Abstract
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Virulence factor gamma-glutamyltransferase (GGT) of H.
pylori consumes glutamine (Gln) in the stomach to decrease
the tricarboxylic acid metabolite alpha-ketoglutarate (α-kg)
and alter the downstream regulation of α-kg as well as cellular
biological characteristics. Our previous research indicated
that under H. pylori infection, mesenchymal stem cells
(MSCs) migrated to the stomach and participated in gastric
cancer (GC) development either by differentiating into epithelial
cells or promoting angiogenesis. However, how MSCs
themselves participate in H. pylori-indicated GC remains
unclear. Therefore, a GGT knockout H. pylori strain (Hp-
KS-1) was constructed, and downstream histone H3K9 and
H3K27 methylation and the PI3K/AKT signaling pathway
of α-kg were detected using Western blotting. The biological
characteristics of MSCs were also examined. An additive α-kg
supplement was also added to H. pylori-treated MSCs to investigate
alterations in these aspects. Compared to the control
and Hp-KS-1 groups, H. pylori-treated MSCs reduced Gln
and α-kg, increased H3K9me3 and H3K27me3, activated the
PI3K-AKT signaling pathway, and promoted the proliferation,
migration, self-renewal, and pluripotency of MSCs. The
addition of α-kg rescued the H. pylori-induced alterations.
Injection of MSCs to nude mice resulted in the largest tumors
in the H. pylori group and significantly reduced tumor sizes
in the Hp-KS-1 and α-kg groups. In summary, GGT of H.
pylori affected MSCs by interfering with the metabolite α-kg
to increase trimethylation of histone H3K9 and H3K27, activating
the PI3K/AKT signaling pathway, and promoting
proliferation, migration, self-renewal, and pluripotency in tumorigenesis,
elucidating the mechanisms of MSCs in GC
development.
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Citations
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