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Impaired bowel movement due to lack of protein

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bild på Sebastian Albinsson and Fatima Daoud.
Sebastian Albinsson and Fatima Daoud. Photo: Agata Garpenlind

Researchers at Lund University have shown that a group of proteins are crucial for smooth muscle function in the gastrointestinal tract. A lack of these proteins leads to a lethal condition called intestinal pseudo obstruction in mice. The findings play a major role in our knowledge of organs that are dependent on normal smooth muscle function such as blood vessels, airways and bladder.

The study is the first to examine the importance of these proteins, called YAP/TAZ, and give an increased understanding of the mechanisms required for gastrointestinal smooth muscle function.

–  When the transcription factors YAP/TAZ are missing in smooth muscle, and therefore bowel movement is impaired, it eventually leads to intestinal obstruction. YAP/TAZ in smooth muscle are guardians of colonic contractility and control expression of contractile proteins and muscarinic receptors. The knockout model has features of human chronic intestinal pseudo-obstruction and may be useful for studying this disease, explains the head of the study, researcher Sebastian Albinsson, from the research group Molecular Vascular Physiology at Lund University, who has led the study.

To function we need to have motility (movement) in the gastrointestinal tract. The proteins that were deleted from the smooth muscle are crucial for this movement.

–Our results describe how the function of the intestines is regulated using YAP/TAZ and this has not been studied in this way before. The study gives us an insight into how the regulation of the smooth muscle that, among other things, perform bowel movements is done.

illustration Albinssons forskning

This means that tissue with smooth muscle such as intestines, but also blood vessels, airways, bladder can have a changed function when YAP/TAZ do not function normally.

 – Our hypothesis is that the strength of the smooth muscle is dependent on YAP/TAZ and that damage to vessels and intestines can occur when tissues lacking YAP/TAZ cannot withstand the stretching of the intestinal contents or blood pressure.

The current study results apply to mice, but reduced YAP/TAZ function due to mutations or drug treatment may result in an increased risk of intestinal or vascular disease in humans. However, it is still unclear whether there is any link between YAP/TAZ and intestinal or vascular disease in humans.

– Now that we know which genes YAP/TAZ regulate in the smooth muscles, we can examine tissue samples from humans and see if we can find patterns for a similar regulation in different types of disease states. We have, for example, a biobank collection of blood vessels from patients with heart disease, which we will now examine in this way.

More information about Sebastian Albinsson in Lund University Research Portal

Publication Cellular and Molecular Gastroenterology and Hepatology

"Inducible Deletion of YAP and TAZ in Adult Mouse Smooth Muscle Causes Rapid and Lethal Colonic Pseudo-Obstruction"
Fatima Daoud, Johan Holmberg, Azra Alajbegovic, Mario Grossi Catarina Rippe, Karl Swärd, Sebastian Albinsson
Cellular and Molecular Gastroenterology and Hepatology, online Sept. 2020, https://doi.org/10.1016/j.jcmgh.2020.09.014

Fact box

Epidemiological research
Study design: Quantitative, researcher-initiated study. Survey study
Observational study: Cross-sectional study
Number of groups in the study: 2 populations (MDCS, Riksmaten), 6 sugar intake groups
Number of patients in the study: 1797 patients from Riksmaten and 12238 patients from MDCS)