Gastric inflammation: How a bacterial infection causes tissue changes


Date:
April 20, 2022
Source:
Charite' - Universita"tsmedizin Berlin
Summary:
When the bacterium Helicobacter pylori infects the stomach, it
causes gastric inflammation and increases the risk of stomach
cancer.

Researchers have been able to elucidate characteristic changes
which occur inside the gastric glands during an H. pylori
infection. The researchers discovered a novel mechanism which, by
restricting cell division in healthy stomach tissue, protects the
stomach against cancerous changes. An inflammation of the stomach,
however, deactivates this mechanism, enabling cells to grow in an
uncontrolled manner. The researchers' findings may herald a new
treatment target in stomach cancer.



FULL STORY ==========================================================================
When the bacterium Helicobacter pylori infects the stomach, it causes
gastric inflammation and increases the risk of stomach cancer. A team
of researchers from Charite' -- Universita"tsmedizin Berlin and the
Max Delbru"ck Center for Molecular Medicine (MDC) have been able to
elucidate characteristic changes which occur inside the gastric glands
during an H. pylori infection. The researchers discovered a novel
mechanism which, by restricting cell division in healthy stomach tissue, protects the stomach against cancerous changes. An inflammation of the
stomach, however, deactivates this mechanism, enabling cells to grow
in an uncontrolled manner. The researchers' findings, which have been
published in Nature Communications, may herald a new treatment target
in stomach cancer.


========================================================================== Affecting about half the world's population, Helicobacter pylori
is one of the most common causes of chronic bacterial infections in
humans. H. pylori can lead to inflammation of the stomach (gastritis)
and increase the risk of developing stomach cancer. As the protective
lining inside the stomach is constantly exposed to stomach acid, it has
to regenerate completely every few weeks, while maintaining both its
structure and composition despite the high cellular turnover. "Until
now, researchers had assumed that a Helicobacterinfection causes
direct damage to the gastric gland cells in the stomach lining and that
gastric pathology upon infection is simply the result of this process," explains the study's last author, Prof. Dr. Michael Sigal. He continues:
"In fact, our team has now discovered that the infection disrupts
complex interactions between different cell types and signals which
are responsible for tissue stability." Prof. Sigal is Professor for Translational Gastrointestinal Oncology and leads an Independent Research
Group at Charite''s Department of Hepatology and Gastroenterology and
the Berlin Institute for Medical Systems Biology (BIMSB), which forms
part of the MDC.

Led by Prof. Sigal and working alongside colleagues from the Max Planck Institute for Infection Biology, the team of researchers used complex
mouse models to observe changes occurring inside the gastric glands. Using state-of- the art imaging and single-cell sequencing technologies, the researchers were able to visualize and isolate specific gastric gland
cells, which they then examined in detail. In order to minimize the
need for animal models, they also developed special organ-like tissue microstructures known as organoids. The researchers used these microscopic stomachs to recreate many of the gastric glands' characteristics. This
strategy enabled them to study the effects of various signals on stem
cells which are found inside the gastric glands (and which are capable
of differentiating into many different cell types).

"We discovered that 'stromal cells' -- a type of cell surrounding the
gastric glands -- are not only responsible for mechanical stability of
the glands, as previously thought. Instead, they produce various signaling molecules which significantly influence the behavior of the gland cells," explains Prof. Sigal.

These substances include 'bone morphogenetic proteins' (BMPs), which play
an important role in tissue development. The researchers were able to
show that stromal cells surrounding the gland base continually inhibit
the BMP signaling pathway, thereby stimulating the proliferation of
nearby stem cells. In contrast, stromal cells at the gland surface
were found to activate the signaling pathway, thereby suppressing
cell proliferation. Together, this forms a signaling gradient that
guides stem cell turnover and differentiation, and serves as the basis
for the gland's structural stability. Helicobacter infection causes
the release of pro-inflammatory substances such as interferon- gamma
(IFN-g). This inflammatory cytokine interferes with the BMP signaling
axis, resulting in less BMP signaling activity and stimulating gland
stem cell proliferation. This results in hyperplasia, a precancerous
lesion characterized by tissue enlargement.

"Our findings show that an infection-driven inflammatory response has far
more pronounced effects than previously thought. In addition to their
well- characterized antimicrobial effects, pro-inflammatory substances
such as IFN- g affect both cell proliferation and tissue stem cell
behavior and therefore have a direct impact on tissue homeostasis. In
the case of tissue damage, increased cell proliferation can be useful,
as it promotes rapid healing. In the case of chronic inflammation
associated with a Helicobacter infection, however, it could facilitate
the development of precancerous lesions," summarizes Prof. Sigal. The
signaling pathways governing interactions between the immune system and
stem cells in the stomach could also prove significant in other organs. As such, they represent a new treatment target -- both in cancer prevention
and regenerative medicine.


========================================================================== Story Source: Materials provided by
Charite'_-_Universita"tsmedizin_Berlin. Note: Content may be edited for
style and length.


========================================================================== Related Multimedia:
* Stomach_tissue_infected_with_Helicobacter_bacteria ========================================================================== Journal Reference:
1. Marta Kapalczynska, Manqiang Lin, Jeroen Maertzdorf, Julian
Heuberger,
Stefanie Muellerke, Xiangsheng Zuo, Ramon Vidal, Imad Shureiqi,
Anne- Sophie Fischer, Sascha Sauer, Hilmar Berger, Evelyn Kidess,
Hans-Joachim Mollenkopf, Frank Tacke, Thomas F. Meyer, Michael
Sigal. BMP feed-forward loop promotes terminal differentiation
in gastric glands and is interrupted by H. pylori-driven
inflammation. Nature Communications, 2022; 13 (1) DOI:
10.1038/s41467-022-29176-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220420133546.htm

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