Research on Integrin α5 Regulates Aldehyde Dehydrogenase 4A1 Expression in Hepatocytes
ZHANG Xuan1,2, CAO Yuqi1, LI Weihong3, LU Xin3, MA Xuqing1, MA Yuejiao1, ZHANG Haiyan1*
This study investigates the effect of ITGA5 (integrin α5) in hepatocytes on the expression of ALDH4A1 (aldehyde dehydrogenase 4A1). DNA hydroxymethylation sequencing, RNA sequencing, and immuno histochemical analysis were employed to examine the impact of specifically targeted knockdown of Itga5 in mouse hepatocytes on the hydroxymethylation level of the ALDH4A1 gene promoter, as well as its mRNA and protein levels. Immunohistochemical staining was used to analyze the protein levels of ITGA5 and ALDH4A1 in liver tis sues from patients with biliary cirrhosis and normal donors. siRNA was utilized to knockdown ITGA5 in human hepatocytes, and real-time quantitative RT-PCR along with immunocytochemical staining were performed to assess the effect of ITGA5 knockdown on ALDH4A1 mRNA and protein levels in human hepatocytes. The results showed that specific knockdown of Itga5 in mouse hepatocytes significantly increased the hydroxymethylation level of the ALDH4A1 gene promoter and its protein level in liver tissues compared to the control group, with a statistically significant difference (P<0.05). Similarly, knockdown of ITGA5 in human hepatocytes also led to significantly higher mRNA and protein levels of ALDH4A1 compared to the control group (P<0.05). In liver tissues from biliary cir rhosis patients, ITGA5 protein levels were lower than those in normal donors, whereas ALDH4A1 protein levels were higher, with statistically significant differences (P<0.05). The study suggests that integrin α5 in hepatocytes may regulate the expression of ALDH4A1 by modulating the hydroxymethylation level of the gene promoter.
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