Yuan, Jason X-J
Mayo Clinic
Center for Inflammation Science and Systems Medicine, Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, University of Florida, Jupiter, FL, United States.
Citations 2
Loss of miRNA-153 promotes EndMT and compromises lung vascular integrity
Elmadbouh, Ibrahim , Zhong, Zhunran, Wang, Li, Chikoore, Stembile, Endoni, Benney, Sah, Aaditya, Thompson, M, Hoeppner, Luke H. , Prakash, Y. S. , Yuan, J, Pabelick, C M, Thompson, Michael A. , Yuan, Jason X.‐J. , Thompson, Michael A , Prakash, Y S , Yuan, Jason X-J , Pabelick, Christina M , Babicheva, Aleksandra , Endoni, Benney T. , Sah, Aaditya, Pabelick, Christina M. , Babicheva, Aleksandra
American Journal of Respiratory Cell and Molecular Biology | May 22, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Endothelial-to-mesenchymal transition (EndMT) is a biological process through which lung vascular endothelial cells (ECs) transdifferentiate into mesenchymal-like cells. EndMT has recently been implicated in the development and progression of pulmonary vascular remodeling in pulmonary hypertension (PH); however, its underlying regulatory mechanisms remain incompletely understood. MicroRNAs (miRNAs) are key post-transcriptional regulators of EC gene expression and cellular responses to various stimuli. Notably, microRNA-153 (miR-153) has been shown to directly target SNAI1 to modulate epithelial-to-mesenchymal transition (EMT), a process closely related to EndMT and extensively studied in cancer. Whether miR-153 also participates in EndMT regulation, however, remains unknown. In this study, we demonstrate that 72-hour hypoxic exposure induces SNAI1-mediated EndMT in human lung vascular ECs. Hypoxia also increased cell proliferation and disrupted intercellular junctions, leading to enhanced endothelial permeability. Reduced miR-153 expression was observed in both hypoxia- and TGF-β1-induced EndMT, as well as in ECs isolated from PH patients exhibiting an EndMT phenotype. Similar to hypoxia, TGF-β1 promoted EC permeability. Loss of miR-153 enhanced SNAI1-mediated EndMT, endothelial survival, and permeability under normoxic conditions, whereas miR-153 overexpression attenuated EndMT induced by hypoxia or TGF-β1. However, miR-153 restoration did not completely restore endothelial barrier integrity disrupted by these stimuli. In vitro findings were validated in experimental PH model. In conclusion, miR-153 serves as a critical regulator of EndMT, maintaining endothelial identity and barrier function. Therapeutic delivery of miR-153 may therefore represent a novel strategy to inhibit EndMT and attenuate pulmonary vascular remodeling in PH.
Store-operated Ca 2+ entry is involved in endothelium-to-mesenchymal transition in lung vascular endothelial cells
Babicheva, Aleksandra , Elmadbouh, Ibrahim , Song, Shanshan , Thompson, Michael A, Powers, Ryan, Jain, Pritesh, Izadi, Amin , Chen, Jiyuan , Yung, Lauren, Parmisano, Sophia , Paquin, Cole, Wang, Ting , Shyy, John Y.-J. , Thistlethwaite, Patricia A. , Makino, Ayako , Yuan, Jason X.‐J. , Shyy, John Y-J , Makino, Ayako , Prakash, Y S , Pabelick, Christina M , Yuan, Jason X-J , Babicheva, Aleksandra , Izadi, Amin, Wang, Wei‐Ting , Chen, Yuqin , Alotaibi, Mona , Shyy, John Y.-J., Wang, Jian , Prakash, Y. S. , Pabelick, Christina M.
American Journal of Physiology-Lung Cellular and Molecular Physiology | May 7, 2025 | Volume: 328 | Issue: 6 | Pages: L844-L857
EndMT has been reported to contribute to the pathogenesis of PAH. In this study, we aimed to determine the role of Ca 2+ signaling in the development of EndMT in human lung vascular endothelial cells. Our data suggest that TGF-β 1 requires store-operated Ca 2+ entry through STIM1/Orai channels to induce SNAI-mediated EndMT. For the first time, we demonstrated that TGF-β 1 -induced EndMT is a Ca 2+ -dependent event, whereas inhibition of STIM1/Orai interaction attenuated EndMT in response to TGF-β 1 .