Abstract： Objective:To explore the role of fibronectin 1(FN1) in the progression of hepatic fibrosis in biliary atresia(BA) and to elucidate its acting mechanism in relation to factors involved in the regulation of apoptotic inositol-3-kinase/protein kinase B(PI3K/Akt)pathway.Methods:The role of FN1 in liver fibrosis was analyzed by bioinformatics using gene database data.Thirty-one liver tissue samples were collected from 3 infants who died from non-hepatobiliary diseases, 5 infants with congenital biliary dilatation(CBD) and 23 BA infants.All liver tissue samples were graded according to the Japanese Ohkuma's liver fibrosis grading standard.According to the degree of fibrosis, BA was divided into two groups: mild fibrosis(Ⅰ~Ⅱ grade)and severe fibrosis(Ⅲ~Ⅳ grade). The expressions of FN1, PI3K, p-Akt and hepatic stellate cell activation marker α-SMA in liver tissue were detected by immunohistochemistry and the correlation between the above proteins and grade of hepatic fibrosis examined.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed for detecting the expression level of FN1mRNA in liver tissues.Results:Bioinformatic analysis revealed that FN1 was highly expressed in liver and it was one of core genes regulating hepatic fibrosis in mice.Expression of FN1 in BA liver tissue: Immunohistochemistry indicated that FN1 was expressed in cytoplasm and extracellular space of BA hepatocytes.The results of semi-quantitative analysis showed that the expression level of FN1 was positively correlated with severity of hepatic fibrosis (r s=0.938, P<0.01). And the expression of FN1 was significantly higher in severe BA group than that in mild BA group [(0.1358±0.0416) vs (0.0548 ±0.0095), t=-6.035, P<0.001]. QRT-PCR quantitative analysis indicated that the expression level of FN1 was also significantly higher mRNA in BA severe hepatic fibrosis group than that in mild hepatic fibrosis group [(1.0530±0.251 0) vs (0.522 1±0.236 5) ng/ml, P<0.01]. Pearson's correlation analysis showed that the expression of PI3K was significantly positively correlated with both upstream and downstream genes of PI3K/Akt pathway, FN1 ( r=0.981, P<0.01) and α-SMA ( r=0.988, P<0.01), in BA liver fibrosis; similarly, the expression of p-Akt was significantly positively correlated with both upstream and downstream genes of this pathway, FN1 ( r=0.946, P<0.01). Similarly, the expression of p-Akt was also positively correlated with the expression of FN1 ( r=0.946, P<0.01) and α-SMA ( r=0.971, P<0.01) in BA liver fibrosis. Conclusions:FN1 in BA liver tissue increases with the aggravation of liver fibrosis and participates in the regulation of liver fibrosis through PI3K/Akt signal pathway.Intervention of FN1 may become a new therapeutic target for BA liver fibrosis.