Fasudil inhibits LPS-induced migration of retinal microglial cells via regulating p38-MAPK signaling pathway.
Year: 2016
Type: article
Abstract: PURPOSE: To investigate the effect and possible molecular mechanisms of fasudil on retinal microglial (RMG) cell migration. METHODS: Primary cultured RMG cells were incubated with lipopolysaccharide (LPS), fasudil, and/or SB203580 (a p38 inhibitor). RMG cell motility was determined with the scratch wound assay and the Transwell migration assay. The phosphorylation of p38 and levels of matrix metalloproteinase 2 (MMP-2) and MMP-9 were measured with western blot. RESULTS: In the scratch-induced migration assay, as well as in the Transwell migration assay, the results indicated that LPS stimulated the migratory potential of RMG cells and fasudil significantly reduced LPS-stimulated RMG cell migration in a concentration-dependent manner. However, fasudil had no effect on RMG cell migration in the absence of LPS stimulation. Moreover, fasudil reduced the level of phosphor-p38 mitogen-activated protein kinase (p-p38-MAPK) in a concentration-dependent manner, without effects on the levels of phospho-p44/42 (p-ERK1/2) and phospho-c-Jun N-terminal kinase (p-JNK). Cotreatment with SB203580 (a p38 inhibitor) and fasudil resulted in the synergistic reduction of MMP-2, MMP-9, and p-p38-MAPK, as well as a reduction in the LPS-stimulated migration capabilities of the RMG cells, suggesting fasudil suppresses the LPS-stimulated migration of RMG cells via directly downregulating the p38-MAPK signaling pathway. CONCLUSIONS: Our studies indicated that fasudil inhibited LPS-stimulated RMG cell migration via suppression of the p38-MAPK signaling pathway.
Source: Europe PMC (PubMed Central)
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2480866744