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dc.contributor.authorZhou, G.A.
dc.contributor.authorRong, L.
dc.contributor.authorKhatib, N.
dc.contributor.authorHuang, J.B.
dc.contributor.authorZhou, Q.
dc.contributor.authorPark, D.
dc.contributor.authorTor, M.
dc.contributor.authorChen, T.
dc.contributor.authorCheng, H.
dc.date.accessioned2016-06-01T21:04:45Z
dc.date.available2017-04-02T09:30:09Z
dc.date.issued2016-04
dc.identifier.bibliographicCitationCheng, H., Chen, T., Tor, M., Park, D., Zhou, Q., Huang, J. B., Khatib, N., Rong, L. and Zhou, G. A High-Throughput Screening Platform Targeting PDLIM5 for Pulmonary Hypertension. Journal of Biomolecular Screening. 2016. 21(4): 333-341. DOI: 10.1177/1087057115625924.en_US
dc.identifier.issn1087-0571
dc.identifier.urihttp://hdl.handle.net/10027/20672
dc.descriptionThis is a copy of an article published in the Journal of Biomolecular Screening © 2015 SAGE Publications.en_US
dc.description.abstractPulmonary arterial hypertension is a complex disease with multiple etiologic factors. PDLIM5, a member of the Enigma subfamily of PDZ and LIM domain protein family, contains an N-terminal PDZ domain and three LIM domains at its C-terminus. We have previously shown that overexpression of PDLIM5 prevents hypoxia-induced pulmonary hypertension (PH), and deletion of PDLIM5 in smooth muscle cells enhances hypoxia-induced PH in vivo. These results suggest that PDLIM5 may be a novel therapeutic target of PH. In this study, we aim to establish a high-throughput screening platform for PDLIM5-targeted drug discovery. We generated a stable mink lung epithelial cell line (MLEC) containing a transforming growth factor-β/Smad luciferase reporter with lentivirus-mediated suppression of PDLIM5 (MLEC-shPDLIM5) and measured levels of Smad2/3 and pSmad2/3. We found that in MLEC, suppression of PDLIM5 decreased Smad-dependent luciferase activity, Smad3, and pSmad3. We used MLEC-shPDLIM5 and a control cell line (MLEC-shCTL) to screen the Prestwick library (1200 compounds) and identified and validated paclitaxel as a PDLIM5 inhibitor in MLEC. Furthermore, we showed that paclitaxel inhibited Smad2 expression and Smad3 phosphorylation in A549 cells. Our study suggests that this system is robust and suitable for PDLIM5-targeted drug discovery.en_US
dc.description.sponsorshipAmerican Lung Association Biomedical Research Grant, a Pulmonary Hypertension Association/Pfizer Proof-of-Concept award (in which American Thoracic Society provides administrative support), an Inception Grant Arm 1 from UIC CCTS and UICentre, a Gilead Sciences Research Scholars Program in Pulmonary Arterial Hypertension award (G Zhou), and NIH R01HL123804 (G Zhou).en_US
dc.language.isoen_USen_US
dc.publisherSAGE Publicationsen_US
dc.subjectTGF/Smaden_US
dc.subjectPDLIM5en_US
dc.subjectluciferase reporter assayen_US
dc.subjecthigh-throughput screeningen_US
dc.titleA high throughput screening platform targeting PDLIM5 for pulmonary hypertensionen_US
dc.typeArticleen_US


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