AsianScientist (May. 02, 2023) – Researchers from Kyushu University in Japan have identified a protein that plays a significant role in fibrosis–a process responsible for wound healing or scarring of tissues by connective tissue deposition. The protein, called VGLL3, was found to contribute to fibrosis in multiple organs. The findings of the study were published in Nature Communications.
Fibrosis is a process characterized by excessive accumulation of extracellular matrix (ECM) proteins, resulting in the formation of fibrous tissue. This happens in response to injury or inflammation and can occur in many different organs and tissues, including liver, lung, heart, kidney, and skin. The ECM can be thought of as a web of proteins that provide structural integrity, just like the beams in a building.
The consequences of fibrosis can be severe, including organ dysfunction and failure, and it is a major contributor to morbidity and mortality worldwide. Some studies indicate that 0.8 million people die every year because of cardiac and lung fibrosis, globally.
When we get injured, our body sends blood cells to the wounded area to stop bleeding and the healing process starts. This healing process around the wound leads to the formation of a scar or scab protecting the wound from infection and allowing new skin cells to grow underneath. Eventually, the scab falls off, and new skin forms over the wound.
However, when an internal organ such as lung or heart is injured because of a forceful blow to the organ, a scab is formed over the injury but may not function as well as the original tissue because the scab stiffens the cells and tissues of the internal organ. In these cases, medications or surgery may be needed to support healing and to restore function.
One type of cell present in ECM is myofibroblasts which produce collagen. “Under diseased conditions, the myofibroblasts overproduce collagen, which ultimately leads to fibrosis in a snowball fashion,” said Michio Nakaya, the corresponding author and associate professor at Kyushu University’s Faculty of Pharmaceutical Sciences, in an article published by the Kyushu University.
The team studied how different physical stimuli change the expression of genes in these myofibroblast cells and noticed a consistent change in the VGLL3 gene expression. In the experiments, the VGLL3 gene produced VGLL3 protein after a heart attack in both human and mouse hearts leading to collagen production. The team also found that fibrotic mouse liver also expressed higher VGLL3 protein levels indicating its role in multiple organ fibrosis. When VGLL3 activation was prevented in mice, the fibrosis was brought under control, which clearly indicated the role of VGLL3 protein in multiple organ fibrosis.
“We found that the inactivation of VGLL3 in mice also reduces the chances of a heart attack after fibrosis,” Nakaya said in the article.
With so few drugs available for fibrosis treatment in the market, the discovery of the role of VGLL3 activation in fibrosis can have great therapeutic potential. “More studies should focus on targeting VGLL3 protein. In the future, we hope to develop therapeutic drugs against fibrosis by targeting the VGLL3 protein,” said Nakaya.
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Source: KYUSHU UNIVERSITY; Image: Shutterstock
The article can be found at: VGLL3 is a mechanosensitive protein that promotes cardiac fibrosis through liquid–liquid phase separation
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