期刊
SMALL
卷 14, 期 49, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201802546
关键词
abnormal fibroblast; mRNA; oligonucleotide sensors; skin disease
类别
资金
- NTU-Northwestern Institute for Nanomedicine
- A*STAR Biomedical Research Council (IAF-PP grant)
- Singapore Ministry of Education Tier-1 Academic Research Funds [RG 131/15]
- Primary Research and Development Plan of Jiangsu Province of China [BE2016770]
Early diagnosis and timely intervention are key for the successful treatment of skin diseases like abnormal scars. This study introduces a nucleic-acid-based probe (i.e., molecular sprinkler) for the diagnosis and spontaneous regulation of the abnormal expression of fibrosis-related mRNA in scar-derived skin fibroblasts. Using mRNA encoding connective tissue growth factor (CTGF) as the model gene, a probe with three oligonucleotides is constructed, including a recognition sequence complementary to the CTGF mRNA, a siRNA against transforming growth factor receptor I (TGF beta RI) as the CTGF mRNA suppressor, and a connecting sequence. The probe can detect CTGF mRNA with a limit of 10 x 10(-9) M and distinguishes scar fibroblasts from normal ones in both 2D and 3D environments. Two days after transfection, the siRNA released from the probe reduces the expression of TGF beta RI and, consequently, decreases the cellular expression of CTGF mRNA (up to 70%). This dual-role probe presents opportunities to monitor the TGF-beta signaling pathway, screen for drugs that target the CTGF pathway, and determine the role of inhibition of the CTGF pathway in therapeutic efficacy.
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