Inhibiting MERTK gene treats fibrosis in multiple organs

Research conducted at The Westmead Institute for Medical Research (WIMR) has revealed that inhibiting a gene called Mer tyrosine kinase (MERTK) can reduce fibrosis in multiple organs. This finding, published in the journal Science Translational Medicine, confirms the role of MERTK in multiple organ fibrosis and could lead to the development of much-needed anti-fibrotic treatments.

Fibrosis is the development of thick, fibrous (or scar) tissue, in response to damage or injury. It can affect every tissue in the body and is associated with most chronic diseases. In cases where excess scarring occurs, organs can lose functionality and even die. Nearly half of all deaths in affluent countries can be attributed to fibrotic diseases — yet despite fibrosis increasingly identified as a global health burden, currently there are no anti-fibrotic treatments available.

“The primary driver behind the process of fibrosis is a protein called transforming growth factor-β (TGFβ),” stated Dr Ziyan Pan, a researcher at WIMR’s Storr Liver Centre. “While it may seem logical to target TGFβ to reduce fibrosis, TGFβ is also involved in many other biological processes, so this makes it difficult to target without impacting its other functions.”

Pan explained that the MERTK gene influences TGFβ function in both human and animal models by promoting signalling that induces fibrosis. With this in mind, the researchers set out to delete it.

“Our research team was able to demonstrate that deleting the MERTK gene in animal models prevented fibrosis from developing in liver, kidney and lungs,” Pan said. “We went on to show that a treatment that inhibits MERKT was able to reduce the severity of existing fibrosis.”

While the study focused on reducing liver fibrosis, Pan noted that the basic process of fibrosis is similar in all organs. Professor Mohammed Eslam, Deputy Director of WIMR’s Storr Liver Centre, noted that finding an anti-fibrotic therapy that is suitable for multiple organs had previously proven to be extremely challenging, so the ability to prevent and reduce fibrosis in the kidneys and lungs as well as the liver was very exciting.

“I feel this is the tip of the iceberg,” Eslam said. “There are many other organs that are susceptible to fibrosis that could benefit from these findings. The potential global impact of these findings is profound.”

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