Mechanism by which imiquimod inhibits the migration of fibroblasts in pathological scars and its targets
Wang Rui1, Lyu Tao1, Huo Jing1, Liu Zhendong1, 2, Song Jianbo1
1Dezhou People’s Hospital, Dezhou 253000, Shandong Province, China; 2Clinical School of Yangzhou University/Subei People’s Hospital, Yangzhou 225001, Jiangsu Province, China
Abstract: BACKGROUND: Studies have shown that imiquimod has a certain prevention and therapeutic effect on pathological scar, but its target and exact mechanism are not clear yet.
OBJECTIVE: To explore and verify the target genes of imiquimod acting on pathological scar, and to observe the effect of imiquimod on the migration ability of scar fibroblasts.
METHODS: Data sets were downloaded from GEO online database and analyzed to screen out the target genes of imiquimod acting on scar tissue. Scar-derived fibroblasts were extracted. The effect of imiquimod on cell migration was detected by cell scratch test and Transwell test. The expression of type 1 collagen and PCOLCE was detected by western blot assay.
RESULTS AND CONCLUSION: By screening the results of data set integration, two target genes, PCOLCE and ARHGEF25, were obtained. The results of cell experiment in vitro showed that compared with the control group, imiquimod treatment group significantly decreased the scratch healing rate and the number of migrated cells (P < 0.05), and the protein expression levels of type I collagen and PCOLCE in scar fibroblasts were also significantly decreased (P < 0.05). The results confirmed that the inhibitory effect of imiquimod on scar may be related to its down-regulation of PCOLCE expression, reduction of extracellular matrix, and reduction of cell migration rate.
Key words: imiquimod, pathological scar, fibroblast, collagen, cell migration