Protein VGLL3 found responsible for increased organ fibrosis
2024-06-18
Fibrosis (fibrosis) is a repair response of the human body to organ or tissue damage. Although fibrosis can quickly compensate for tissue damage and protect the integrity of tissues and organs, due to the proliferation of fibrous tissue does not have the structure and function of the original organ cells, excessive and uncontrolled fibrosis will still lead to tissue dysfunction. In developed countries, about 45% of deaths are related to organ fibrosis, and there are currently no drugs that can effectively combat fibrosis.
In the new Nature Communications study, the Kyushu University (Kyushu University) team first found that a mechanosensitive protein called VGLL3 (mechanosensitive protein) induces the process of thickening and scarring tissue, which is expected to lead to the emergence of new anti-fibrosis treatments.
Extracellular matrix (extracellular matrix, ECM) is a protein network in every cell of the body. At the same time, it has many functions such as allowing cells to communicate with each other and providing structure for organs. When organs or tissues are damaged, extracellular matrix will be secreted to help tissues heal. Excessive extracellular matrix will harden cells and tissues and promote organ fibrosis.
In diseased organs, myofibroblasts (Myofibroblasts) overproduce collagen, one of the main components of the extracellular matrix, allowing fibrosis to unfold in a snowball-like manner. To understand how myofibroblasts turn into pathological conditions, the Kyushu team applied different physical stimuli to the mouse model and observed how gene expression changed in the cells, eventually finding a consistent change in the expression of one of the genes: VGLL3.
During a heart attack, myofibroblasts in mouse and human hearts express more VGLL3 protein, which leads to collagen production. VGLL3 expression was also found to be higher in mice with fibrotic livers. Subsequent attempts to block VGLL3 activation have also been shown to reduce fibrosis in these organs, showing that VGLL3 is indeed involved in fibrosis in multiple organs.
The researchers found that mechanical stimulation of myofibroblasts (mechanical stimuli) stimulates VGLL3 activation to produce collagen leading to tissue hardening, which in turn leads to increased mechanical stimulation, which again induces VGLL3 activation to stimulate more collagen production, thus continuously forming a pathological cycle that leads to increased fibrosis.
Considering the effect of VGLL3 mediated pathway on fibrosis, the researchers believe that relevant research should be more invested in exploring this protein. At present, only a few drugs can be used to treat fibrosis, and each has its own limitations. The research team hopes that VGLL3 can be used as a potential target in the future, which will further contribute to the development of drugs and therapies for fibrosis treatment.
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