Recently, Professor Rao Yi, the Capital Medical Science Innovation Center/Capital Medical University, published in "Science Advances" entitled "Discoveries of GPR39 AS An Evolutionarily CONSERVED RecePTOR BILE BILE BILE BILE BILDS AND of its involvement in biliary Research papers of Acute Pancreatitis ".The results of the study show that the "orphan receptor" GPR39 is a conservative receptor in the evolution of bile acid (BA) (especially 3 Ob sulfuric acid bile acids), which can mediate the elevated calcium ionic concentration caused by BA and blisters. Death, knockout GPR39 can significantly reduce gallbladder acute pancreatitis, thereby providing hopeful treatment targets for the prevention and treatment of such diseases.Zizhentao is the first author, and Professor Rao Yi is the author.
Acute pancreatitis is a severe and severe gastrointestinal disease. The hospitalization rate and disease mortality rate is extremely high, but the pathogenesis mechanism is not completely clear.Previous studies have shown that bile acids damage the pancreatic glandular blisters by calcium dependence, and start the occurrence and development of acute pancreatitis.But bile acid is unclear to play the biological effect by combining the receptor.
G protein coupling recovery (GPCR) is the most important cross -diaphragm protein that mediates internal and external communication.The team first analyzed the GPCR expressed in the heights in the glandular cells and transformed it stably in the tool cells. The results showed that the steady transfer of GPR39 can mediate TLCAS (secondary bile acids from petroleum acid LCA) Internal calcium increased, and TLCAS activated GPR39 in dose-dependency mode; then the team studied the activation of different bile acids on GPR39. As a result, when there was no ZN2+, the three-O-sulfuric acidization LCAs could significantly activate GPR39. When ZN2+exists, all bile acids except LCA can activate GPR39, and bile acids and Zn2+promote the activation of GPR39; evolving tree analysis shows that GPR39 evolved from bile acid receptor to bile acid and Zn2+receptor.These results suggest that GPR39 is sufficient for bile acid activation.Next, the team studied GPR39 through the inside and outside knockout experiment. The GPR39 was necessary to increase the CA2+of the pancreatic glandocytes induced by bile acid.Tap/knockout GPR39 can significantly inhibit TLCAS stimulating glandular cell amylase secretion, and inhibit the acute pancreatitis process (edema, inflammation, and necrosis of bile acid -induced acute pancreatic inflammation processes, reduced amylase and lipase in serum).
GPR39 The activation effect of bile acid
The above The study and identification of "orphan receptors" GPR39 is a new receptor for the evolution of bile acid. It can participate in acute pancreatitis induced by bile acid, which provides potential new targets for the prevention and treatment of clinical gallbladder acute pancreatitis.
This study is funded by the capital of the Capital Medical Science Innovation Center and Changping Laboratory.
Full -text link : https://www.science.org/doi/10.1126/sciadj0146
Source: Capital Medical University
