Targeting Fibrosis

Fibrosis is the pathological overaccumulation of excess connective tissue as a result of imbalances during the body’s healing processes following an injury, whether chronic or acute, from activated myofibroblasts. The shift from appropriate wound healing to pathological fibrosis occurs as the rate of extracellular matrix deposition outstrips the rate of degradation. This results in thickened less elastic tissue, scar formation, reduced organ function, and ultimately organ failure. Epidemiologic data shows that nearly 45% of all deaths in the developed world are attributed to chronic fibroproliferative diseases and with only two drugs approved by the FDA for treatment, there is clearly an unmet clinical need.

Fibrosis affects every organ in the body, but it can be commonly found in the lungs (i.e. pulmonary fibrosis), the eye (i.e. macular degeneration) and the liver (i.e. non-alcoholic fatty liver disease). Although the causes are not always known exactly, they can be broadly grouped into reactions to continuous stimuli, for example an autoimmune response, chronic disease, or long-term exposure to pollutants and toxins.

The epithelial mesenchymal transition is implicated as the mechanism behind the increase in myofibroblasts as epithelial cells transition to deal with the tissue injury. In the liver, transforming growth factor-β1 has been shown to downregulate epithelial markers (E-Cadherin, Zonula Occludens Protein-1) while upregulating mesenchymal marker expression (Collagen, Smooth Muscle Actin, Vimentin). This can provide some insight into the mechanism behind fibrosis and shows myofibroblasts as a potential therapeutic target. The challenge lies in the disentangling of the normal healing response from the pathological.

If you are interested in targeting fibrosis with best-in-class in vitro assays or quantifying fibrosis from tissues or traditional two-dimensional tissue sections, reach out to Visikol. We have developed in vitro models of fibrosis and are ready to design a disease model for you.

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2019-10-01T20:26:27-05:00Tags: |

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