遗传性酶紊乱导,纤维化 z-bo 2020-10-08 287

　　In a study completed by scientists at St. Jude Children’s Research Hospital, and recently published in the journal Science Advances, researchers found that the deficiency of neuraminidase 1 (NEU1) is associated with muscle, kidney, liver, heart and lungs. Joint related. (Fibrosis) is related to formation. Fibrosis includes life-threatening diseases, such as idiopathic pulmonary fibrosis. EU1 gene mutations cause liposome storage sialic acidosis is the main type of childhood diseases. Its corresponding author, Dr. Alessandra Dazzo, head and chair of the Department of Genetics at St. Jude Children’s Research Hospital, said: “This is the first time that NEU1 has been linked to fibrotic diseases.” “EU1 is an important enzyme that can break down many cells in the human body. Sugar molecules, but due to adult health issues, it has not yet attracted people’s attention."

　　She said: “Based on these findings, NEU1 expression levels may help identify individuals at risk of fibrosis and inform prognosis, especially when there is a lack of information about the cause and possible treatments. “If too much connective tissue is produced , When the normal function of muscles, lungs, liver, heart and other tissues accumulate and destroy, fibrosis will occur.

　　early evidence

　　These findings are based on an early study by the Azzo Institute, which focused on mice lacking the Neu1 gene. With the proliferation and invasion of connective tissue, the muscles of mice atrophy. In this study, the researchers found that mouse fibroblasts lacking Neu1 can proliferate, migrate and release many molecules. Azzo said: "These cells have begun to function like cancer cells." He revealed the mechanism that promotes the continuous expansion of connective tissue, thus revealing its underlying mechanism. She has previously reported on the potential role of NEU1 deficiency in cancer, especially in connective tissue carcinosarcoma. The researchers found that mouse fibroblasts lacking Neu1 release too many molecules to degrade the extracellular matrix and small vesicles (exosomes). Exosomes are rich in factors that promote fibrosis, such as growth factor TGF-β and signaling molecule WNT. When exposed to exosomes containing TGF-β, WNT and related molecules released by hypoxic fibroblasts, normal mouse and human fibroblasts are activated to proliferate and migrate.

　　human disease

　　Researchers examined the tissues of adults with idiopathic pulmonary fibrosis and found that the production of NEU1 was significantly reduced (down-regulated) compared with undiagnosed adults. Find. The researchers checked the RNA sequencing database of 89 idiopathic pulmonary fibrosis patients and found that NEU1 was one of the most down-regulated genes among the 66 genes in the database.

　　According to research, NEU1 deficiency is related to catastrophic diseases in children, and may be a risk factor for the development and progression of adult fibrotic diseases. The main reason is unclear. These findings also support Dazzo’s belief that detailed studies of rare childhood diseases (such as liposome storage disorders) often help explain underlying disease mechanisms common to older adults.