Abstract
AbstractAs important mediators of intercellular communication, exosome have can modulate various cellular functions by transferring a variety of intracellular components to target cells. However, little is known about the role of exosome-mediated communication between distant organs. Hepatopulmonary syndrome (HPS) is a severe lung injury caused by chronic liver disease. A new long noncoding RNA (lncRNA) PICALM-AU1 was found and upregulated in the liver of HPS. It was located in the cholangiocytes of liver and then, secreted as exosome into the serum. PICALM-AU1 carrying serum exosomes induced endothelial-mesenchymal transition (EndMT) of PMVECs and promoted lung injury in vivo and in vitro. Furthermore, overexpression of PICALM-AU1 significantly suppressed miR144-3p and subsequently induced ZEB1 expression. Taken together, our findings identified cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the EndMT of HPS lung. And PICALM-AU1 represents a noninvasive biomarker and potential therapeutic target for HPS.
Publisher
Cold Spring Harbor Laboratory
Reference48 articles.
1. Hepatopulmonary Syndrome — A Liver-Induced Lung Vascular Disorder
2. Fallon MB , Krowka MJ , Brown RS , Trotter JF , Zacks S , Roberts KE , Shah VH , Kaplowitz N , Forman L , Wille K et al : Impact of hepatopulmonary syndrome on quality of life and survival in liver transplant candidates. Gastroenterology 2008, 135(4):1168–1175.
3. The angiogenic related functions of bone marrow mesenchymal stem cells are promoted by CBDL rat serum via the Akt/Nrf2 pathway;Experimental Cell Research,2016
4. AMD3100 treatment attenuates pulmonary angiogenesis by reducing the c-kit (+) cells and its pro-angiogenic activity in CBDL rat lungs;Biochimica et biophysica acta,2017
5. Lejealle C , Paradis V , Bruno O , de Raucourt E , Francoz C , Soubrane O , Lebrec D , Bedossa P , Valla D , Mal H et al: Evidence for an association between intrahepatic vascular changes and the development of hepatopulmonary syndrome. Chest 2018.