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Inhibition of protein could reduce scar formation

22 June 2016

A research group from the UMCG is the first to develop a method to block the protein LH2. LH2 is responsible for the formation of scar tissue, which can cause liver and lung fibrosis or chronic kidney disease. The group discovered that another protein, FKBP65, activates LH2 and that the drug Tacrolimus blocks FKBP65. This is the first time that a potential treatment for internal fibroses and disfiguring scars has been found. The researchers have published their findings in PNAS.

Collagen accumulates in scars, in part because it does not break down easily. Collagen can bind together in two different ways. The enzyme lysyl hydroxylase 2 (LH2) forms tough bonds that do not break down easily. As a lot of LH2 is present in scars, many of these tough bonds can be made, causing the collagen to accumulate. In internal organs, this kind of scar (fibrosis) can block vital functions and lead to death. Examples of this are liver fibrosis, lung fibrosis and chronic kidney disease. Many chronic diseases in the Western world are the result of this increased tissue formation, where tough collagen that does not break down easily replaces functional tissue.

LH2 not activated

There is no known inhibitor for LH2. However, prior research in patients with the extremely rare Bruck Syndrome has shown that another protein, FKBP65, does ‘something’ to LH2. These patients lack LH2, and as a result their bones degenerate rapidly. The research group of biomedical researcher Ruud Bank has now discovered that FKBP65 activates LH2 and has established how this process works. If no FKBP65 is present, the LH2 that has been made in scar tissue is not activated and the collagen does not form tough bonds. The reasearchers also discovered that the drug Tacrolimus blocks FKBP65. As FKBP65 activates LH2, this could prove an ingenious way to inhibit LH2. So for the first time there is a potential treatment that could turn the tough collagen bonds into soft ones.

Follow-up studies

Follow-up studies will use the new knowledge to investigate whether and how such treatment could be used. It is noteworthy that Tacrolimus is used to treat other symptoms: eczema patients use it to reduce itching and swelling because it inhibits the immune system and inflammation at the site of this itching and swelling. The newly discovered function of Tacrolimus means that it could also be used to combat fibrosis, which would reduce disfiguring scars in burn patients and ensure the proper functioning of internal organs.

Link to the publication in PNAS: http://www.pnas.org/content/early/2016/06/07/1600074113.full?sid=7dd8f656-2db6-4199-8b41-c98067cbe6e1

Source: press release UMCG

Last modified:12 March 2020 9.40 p.m.
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