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| Lnc-FOXD3-AS1 Promotes the Expression of Ferrimodulin in Rats with Iron Deficiency Anemia by Activating SMAD1/5/8 |
| ANYUANYUAN Anlin, JI Yanmin, et al |
| The Seventh Affiliated Hospital of Xinjiang Medical University, Xinjiang Urumqi 830000, China |
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Abstract Objective: To investigate the regulatory effect of long-chain noncoding RNA FOXD3-AS1 (Lnc-FoxD3-AS1) on the expression of hepcidin in rats with iron deficiency anemia (IDA). Methods: The IDA model was induced by repeated bloodletting and feeding low iron diet to SD rats without specific pathogen grade. The rats were divided into control group, IDA group, IDA rats treated with LCN-FoxD3-AS1 overexpression group (pcDNA-FOXD3-AS1+IDA group), IDA rats treated with empty vector expression group (pcDNA-null+IDA group), and IDA rats treated with pcDNA-FOXD3-AS1 combined with Sm ad1/5/8 activation inhibitor Compound C treatment group (pcDNA-FOXD3-AS1+Compound C+IDA group), n=8 for each group. The content of iron in blood of rats in each group was detected by kit method, the expression of Lnc-FOXD3-AS1 in liver tissue and serum was detected by qRT-PCR, and the expression and activation of ferrimodulin and SMAD1/5/8 protein in liver tissue and serum were detected by western blot and ELISA. Results: Iron deficiency anemia model was successfully induced in IDA group. Compared with the control group, iron content in liver tissue and serum of rats in IDA group remained in the state of iron deficiency (all P<0.05), and the expression levels of ferrimodulin, LCNC-FOXD3-AS1 and SMAD1/5/8 were significantly decreased (all P<0.05), and the phosphorylation level of SMAD1/5/8 was significantly decreased (all P<0.05). Compared with pcDNA-null+IDA group, iron content in liver tissue and serum in pcDNA-FOXD3-AS1+IDA group was significantly increased (all P<0.05), and the expression levels of ferrimodulin, LCNA-FOXD3-AS1 and SMAD1/5/8 were significantly increased (all P<0.05). Moreover, the phosphorylation level of SMAD1/5/8 was significantly increased (P<0.05). Compared with pcDNA-FOXD3-AS1+IDA group, the iron content in liver tissue and serum of pcDNA-FOXD3-AS1+Compound C+IDA group was significantly decreased (all P<0.05), and the expression levels of ferromodulin and SMAD1/5/8 were significantly decreased (all P<0.05). Conclusion: lnc-FOXD3-AS1 is downregulated in the IDA rat model, and it promotes the expression of Hepcidin by activating the SMAD1/5/8 pathway. This study is of great significance for a deeper understanding of the biological network mechanisms underlying IDA occurrence.
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2023, Vol. 29 
