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Source: University of Michigan  Feb 28, 2019  3 years ago
Scleroderma fibrosis could be prevented by inhibiting cancer-causing protein
Scleroderma fibrosis could be prevented by inhibiting cancer-causing protein
Source: University of Michigan  Feb 28, 2019  3 years ago

A protein molecule called EZH2,  known to play a role in cancer may also be increasing fibrosis in scleroderma patients.

scleroderma fibrosis

Studies and researches that have been made show that Scleroderma, a rare chronic autoimmune disease, causes difficulties during breathing, exhaustion and most concerningly hardens the internal organs and the skin.

“Tissues and organs are damaged due to the disease as a result of excessive fibroblast being activated.” Explained  Amr Sawalha, M.D., a professor in the Division of Rheumatology at the University of Michigan in an exclusive interview with Thailand Medical News.

Sawalha and his collaborators examined scleroderma  at the molecular level to better understand the fibrosis course. This was published in Proceedings of the National Academy of Sciences

Sawalha says "We analyzed the molecule EZH2, which has been known to play a certain role in several types of cancer," "This particular protein collocates gene expression  by affecting modifications that happen to DNA and other proteins attached to DNA, owing to a process called epigenetic regulation."

Sawalha and his co-workers in this curious research had found out and identified a role for EZH2 in lupus, which is a different autoimmune disease.

"EZH2 is emphasized in lupus T cells, which activates these white blood cells in lupus patients," Sawalha says. "We then increased our studies to scleroderma and especially looked at the role of EZH2 in fibroblasts and endothelial cells  in this disease."

Studying  EZH2

First the research team isolated cells from scleroderma patients in cooperation with the Michigan Medicine Scleroderma Program. This specific program supplies care for a large number of scleroderma patients at the University of Michigan. The studies then expanded to animal models to and further examinations discovering in the human cells.

"In this autoimmune disease, increased fibrosis and abnormal blood vessel function, or defective angiogenesis, were observed and both are major aspects of pathology. says Eliza Tsou, Ph.D., a research assistant professor at U-M and first author of the study stated that. "We dissected the cells and found that increased levels of EZH2 were contributing to this disease process in scleroderma patients."

Once the molecule was identified, the research team tested what happened in the cells when EZH2 was inhibited.
Sawalha added "When we suppressed EZH2, we found we could correct increased fibrosis and abnormal blood vessel function in scleroderma,"
Sawalha says the ability to translate their laboratory work to patients may be easier, due to the fact that the molecule known to play a part in cancer patients.

He added "The great thing is that EZH2 inhibitors are already developed and are in  clinical trials  stages in certain cancers,” “Therefore, our findings can be more smoothly translated to the patients by repurposing already available inhibitors for EZH2 to treat scleroderma."

Sawalha points out that this type of research is important for future studies due to the fact that there are no other realistic treatment options for the disease.

Sawalha says; "We will keep researching this disease at the molecular level and do our best to identify expanded therapeutic targets for these patients,"


Pei-Suen Tsou et al, Inhibition of EZH2 prevents fibrosis and restores normal angiogenesis in scleroderma, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1813006116


Feb 05, 2020  2 years ago
Source : Thailand Medical news