Scientists Uncover Repair Properties of Key Gut Wound-Healing Protein

Scientists have reported their discovery of the properties of a key protein that aid in the repair of the gastrointestinal tract (GI) cell lining in patients with gut disorders.

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The new study, which appeared in Cell, provides useful insights on the mechanisms underlying the repair of gastrointestinal tract cells by the protein Gasdermin B in chronic inflammatory disorder patients. It helps to understand better the effect of this protein as regards the healing of epithelium, which lines organs with direct contact to the outer environment.

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Findings could aid further research into gut wound healing as well as the development of new drugs that can help with this.

The study was carried out by a team of international scientists, including gastroenterologists, cell biologists, immunologists, and bioinformaticians.

The role of gasdermins in gut diseases

The gasdermin (GSDM) family of proteins is mainly known for causing cell death. Researchers know these proteins as mediators of pyroptosis, which is cell death often brought about by inflammation or infections.

Inflammation is a big problem in the incidence of gut disorders, such as Crohn’s disease and ulcerative colitis.

However, Gasdermin B (GSDMB) stands out in this protein family. It does not trigger pyroptosis, particularly in epithelial cells, unlike the others. Rather, this protein helps to boost the health of the GI tract.

Scientists have also shown in previous research that certain genetic variants of GSDMB increase the risk of inflammatory disorders, such as inflammatory bowel disorder (IBD) and asthma.

Researchers knew little about how this happened. But current study’s lead author Theresa Pizarro said their studies have now shown the “functional consequences of these GSDMB genetic variants.”

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According to her, IBD patients may have higher GSDMB levels during flares. But the protein produced by these genetic variations inhibits the restorative capacity of epithelial cells. This blocks healing in ulcerative colitis patients as an example.

Key processes

Pizarro and her colleagues obtained samples from patients with Crohn’s disease and ulcerative colitis. Next, they carried out analyses on these using advanced techniques, including epithelial organoid cultures, CRISPR/Cas9, and single-cell RNA sequencing.

The team observed significantly higher GSDMB levels in biopsies of patients with IBD, compared to levels in healthy individuals. This was especially so with ulcerative colitis.

Researchers were surprised to observe the absence of cell death. Higher GSDMB levels advanced the proliferation and migration of cells as well as reduced adhesion dynamics.

These processes combine to enhance epithelial layer restoration and proper wound healing, according to researchers.

The findings could prove highly helpful in research for new therapeutics for wound repair in gut diseases.

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“Future therapies targeting gasdermin B are not necessarily restricted to IBD or other chronic inflammatory states of the gastrointestinal tract,” said Pizarro, who is the Louis Pillemer Professor of Experimental Pathology at the Case Western Reserve University School of Medicine.

She said such treatments could also have “far-reaching implications” for promoting efficient wound-healing in organs, including lungs and skin, which interface with the external environment and require having a functional epithelial layer.

Apart from the Cape Western Reserve University, Cleveland Clinic Lerner Research Institute was among the institutions represented in this study. Others included Oxford University, Baylor College of Medicine, and the University of Athens.

References

GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis

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