Dr. Shui, Jr-Wen ’s Lab徐志文 博士 實驗室

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Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas

Nature Communications, Aug 27, 2020

Galectin-9 is a risk factor for inflammatory Crohn’s disease in the gut. Our research reveal glycosylation of lysosomal membrane proteins in lysosomes of Paneth cells provides binding sites for galectin-9. Such interaction not only stabilizes lysosomes but also maintains functionality of autophagy, which prevents gut inflammation. Similar galectin-9-mediated function was identified in pancreatic acinar cells. Loss of galectin-9 in mice causes spontaneous pancreatitis and fibrosis. Therefore, lysosome dysfunction confers increased susceptibility to pathogenesis in the gut and pancreas. Our findings explains why a portion of patients with inflammatory bowel disease (IBD) have clinical extraintestinal manifestations (EIMs) such as pancreatic disorders.  

半乳糖凝集素-9 (Galectin-9) 為腸道克隆氏症 (Crohn‘s disease) 的風險因子.我們的研究首度揭示潘氏細胞 (Paneth cell) 內溶酶體 (lysosome) 的醣基化,不僅提供與半乳糖凝集素-9的鍵結,同時也增強溶酶體的結構及穩定潘氏細胞自噬功能 (autophagy),藉此維護潘氏細胞的功能,而避免腸道發炎.相同的調控機制也發生在胰臟的腺泡細胞 (acinar cell), 我們發現小鼠半乳糖凝集素-9 缺失會導致自發性胰臟炎及纖維化.因此,溶酶體功能缺失有可能會同時引發腸道及胰臟病變,這結論解釋了為何腸道發炎病人有些會有胰臟病變的臨床病徵.

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