BackgroundMyocardial fibrosis is an important pathological change in many heart diseases, but its pathogenesis is very complex and has not yet been fully elucidated. The study was designed to examine whether endogenous sulfur dioxide (SO) is a novel myocardial fibroblast proliferation and migration inhibitor.

MethodsPrimary rat myocardial fibroblasts were isolated and transfected with aspartate aminotransferase (AAT1 and AAT2) knockdown lentivirus or empty lentivirus. SO content in the supernatant was determined with high-performance liquid chromatography, and the expressions of AAT1, AAT2, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated protein kinase (p-ERK), and total ERK (T-ERK) in the cells were detected. Cell migration was detected by wound healing test. Independent sample t-test (for two groups) and one-way analysis of variance (three or more groups) were used to analyze the results.

ResultsBoth AAT1 and AAT2 knockdown significantly reduced SOlevels (F = 31.46, P < 0.01) and AAT1/2 protein expression (AAT1, t = 12.67, P < 0.01; AAT2, t = 9.61, P < 0.01), but increased PCNA expression and Cell Counting Kit-8 (CCK-8) activity as well as the migration in rat primary myocardial fibroblasts (P < 0.01). Supplementation of SOrather than pyruvate significantly inhibited the increase in proliferation and migration caused by AAT knockdown (P < 0.01). Mechanistically, the ratio of p-ERK to T-ERK was significantly increased in the AAT1/2 knockdown groups compared with that in the empty lentivirus group (AAT1, t = -7.36, P < 0.01; AAT2, t = -10.97, P < 0.01). Whereas PD98059, an inhibitor of ERK activation, successfully blocked AAT knockdown-induced PCNA upregulation (F = 74.01, P > 0.05), CCK-8 activation (F = 50.14, P > 0.05), and migration augmentation in myocardial fibroblasts (24 h, F = 37.08, P > 0.05; 48 h, F = 58.60, P > 0.05).

ConclusionEndogenous SOmight be a novel myocardial fibroblast proliferation and migration inhibitor via inhibiting the ERK signaling pathway.