Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, most fibrosis treatment strategies are restricted to specific diseases or organs. However, evidence is accumulating showing strong similarities between fibro proliferative diseases, and a growing number of drugs are proving to be effective antifibrotic therapies in a variety of diseases and organs. , comprehensively reviews current knowledge on the pathological mechanisms of fibrosis and partitions the factors that mediate fibrosis progression into extracellular and intracellular groups. In addition, we systematically summarize both single-component and multi-component drugs targeting fibrosis. The future direction of fibrosis drug discovery is also suggested.

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Fibrosis, characterized by excessive accumulation of Extracellular Matrix (ECM), is a common pathological process in many chronic diseases or injuries. Many stimuli provoke profibrotic responses, including persistent infections, radiation, chemicals, genetic diseases, and autoimmune diseases. The development of fibrosis involves the loss of some of the resident cells and their replacement by the ECM, ultimately leading to tissue remodeling and organ failure. Fibrosis contributes to high morbidity and mortality in many diseases, such as dilated cardiomyopathy and idiopathic pulmonary fibrosis (IPF), and inevitably poses a significant global clinical burden. For example, a study of the Medicare population aged 65 and older showed that the incidence of IPF was about 93.7 cases per 100,000 person-years, whereas the cumulative prevalence in the United States was 2001–2011. Furthermore, patients with non-alcoholic fatty liver disease (NAFLD) with more likely fibrosis had a 69% higher mortality rate than those without fibrosis.

As a long-lasting pathological phenomenon, fibrosis occurs in a variety of tissues and organs, but more commonly in the heart, lungs, kidneys, liver, skin, pancreas, intestines, eyes and nervous system.. Fibrosis contributes to the development of many diseases. First, many studies have shown that the central mechanisms of fibrosis are similar in different tissues and organs. We found that interactions between growth factor signaling are required for kidney, liver and lung fibrosis. Based on the common etiology of fibroproliferative diseases, several new drugs have been shown to be effective in treating fibrosis in various tissues and organs. For example, pirfenidone is in Phase II clinical trials for the treatment of systemic sclerosis (SSc) and in Phase III trials for IPF. The interferon drug Actimmune is being studied in patients with IPF, liver, and cystic fibrosis.

Second, multiple fibrotic diseases are associated with different tissues and organs. They are usually triggered by the same stimulus and occur simultaneously. For example, the heart and kidney develop fibrosis (cardiorenal fibrosis) with age due to an imbalance between the natriuretic peptide system and the renin-angiotensin-aldosterone system/TGF-β1 pathway. Chronic or acute renal failure can lead to renal systemic fibrosis, which progresses from skin thickening to visceral damage. Furthermore, cystic fibrosis caused by genetic mutations can severely affect multiple organs such as lungs, kidneys and pancreas. Moreover, fibrosis is a common pathological process in NAFLD and inflammatory bowel disease. Replacing cardiac tissue with fibrous proteins can alter the size and shape of the ventricles, leading to hypertrophic cardiomyopathy. Cancers such as hepatocellular carcinoma share many risk factors with liver fibrosis.

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Emma Roberts

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Journal of Developing Drugs
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