Two new candidates have been identified as crucial factors in maintaining good intestinal health.
An international team led by Hudson Institute of Medical Research investigating so-called Mediator kinases – regulators of gene expression – discovered that they play a bigger than expected role in maintaining a proper balance of the different cell populations that make up the intestinal lining.
In a study, published in the Journal of Clinical Investigation (JCI), with wide-ranging implications for inflammatory conditions affecting the intestine, the team found that Mediator kinases also interact with another group of proteins which have been linked to many diseases and cancers.
Intestinal health requires a balance of cell types
Post-doctoral researcher Dr Danxi Zhu said this project has potential implications for a number of gastrointestinal disorders including bowel cancer.
“That’s big news by itself, however we also believe it provides the foundation for further investigations into disease relevance and potential suitability for the development of new treatments,” Dr Zhu said.
“We discovered that Mediator kinases play a pivotal role to orchestrate the production of the cells lining the intestinal lumen, particularly for specialised cell types (Paneth cells, tuft cells and goblet cells) responsible for organising the defence against infection.
“Malfunction of these cell types has been linked to increased susceptibility to bacterial and parasitic infections and inflammatory conditions such as Inflammatory Bowel Disease (IBD).” she said.
Reading intestinal health like a book
Dr Marius Dannappel explained the workings of the Mediator kinases: “If the genetic code (DNA) is a book, the Mediator complex is one of the components that determines which parts of the book are read and read correctly.”
“That means we’ve changed the previous view of Mediator kinases as purely regulators of gene expression and significantly broadened the scope of their functions,” he said.
Potential in cancer and beyond
“The aim for follow-up studies will be to assess whether Mediator kinases could be targeted therapeutically to treat inflammatory conditions affecting the intestine including cancer,” he said.
Collaborators | Professor Thomas G Boyer, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, Texas, USA; Pouya Faridi, Department of Medicine, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University; Professor Roger J Daly, Cancer Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University.
Funders | NHRMC; DFG (German Research Foundation); China Scholarship Council
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