title: Role of P38 MAPK on MMP Activity in Photothrombotic Stroke Mice as Measured using an Ultrafast MMP Activatable Probe.
abstract: Matrix metalloproteinases (MMPs) exert a dual effect in ischemic stroke and thus represent an ideal target for detection and therapy. However, to date, all clinical trials of MMP inhibitors have failed, and alternative drug candidates and therapeutic targets are urgently required. Nonetheless, further investigations are limited by the lack of non-invasive imaging techniques. Here, we report a novel, fast and ultrasensitive MMP activatable optical imaging probe for the dynamic visualization of MMP activity in photothrombotic stroke mice. This probe provides a significant signal enhancement in as little as 15 min, with the highest signal intensity occurring at 1 h post-injection, and shows high sensitivity in measuring MMP activity alterations, which makes it specifically suitable for the real-time visualization of MMP activity and drug discovery in preclinical research. Moreover, using this probe, we successfully demonstrate that the regulation of the p38 mitogen-activated protein kinase (MAPK) signal pathway is capable of modulating MMP activity after stroke, revealing a novel regulatory mechanism of postischemic brain damage and overcoming the limitations of traditional therapeutic strategies associated with MMP inhibitors by using a non-invasive molecular imaging method.
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Chang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Yuan-Cheng
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Bai
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Chun-Qiang
authors.initials: CQ
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics &Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, 361005, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Shenghong
authors.initials: S
authors.lastname: Ju
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D008027:Light; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D015335:Molecular Probes / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects; D019265:Spectroscopy, Near-Infrared; D020521:Stroke / Q000201:enzymology* / Q000209:etiology* / Q000503:physiopathology; D013927:Thrombosis / Q000150:complications* / Q000473:pathology; D014018:Tissue Distribution / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D015335:Molecular Probes; D048051:p38 Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases