This study investigates the protective mechanism of miR-223-3p in bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) against HBx-induced ferroptosis in renal podocytes. The research aims to understand how miR-223-3p targets HDAC2 to downregulate STAT3 phosphorylation, thereby alleviating podocyte injury. Key findings include: 1. **STAT3 Phosphorylation and Ferroptosis**: Inhibition of STAT3 phosphorylation significantly reduces HBx-induced ferroptosis in podocytes, as evidenced by improved cell viability, reduced lipid peroxidation, and decreased mitochondrial damage. 2. **HDAC2 and STAT3 Phosphorylation**: HDAC2 overexpression enhances STAT3 phosphorylation, promoting ferroptosis. In contrast, HDAC2 inhibition or miR-223-3p overexpression in BMSC-Exo reduces STAT3 phosphorylation and ameliorates ferroptosis. 3. **BMSC-Exo and Podocyte Protection**: BMSC-Exo carrying miR-223-3p effectively suppresses HDAC2 expression, leading to reduced HBx-induced ferroptosis in podocytes. This effect is mediated through the downregulation of STAT3 phosphorylation. 4. **Animal Model and In Vivo Validation**: In HBx transgenic mice, treatment with BMSC-Exo containing miR-223-3p significantly reduces renal damage, increases podocyte markers, and decreases ferroptosis-related markers. 5. **Conclusion**: The study demonstrates that BMSC-Exo-mediated delivery of miR-223-3p can effectively mitigate HBx-induced ferroptosis in podocytes, offering a novel therapeutic approach for treating hepatitis B virus-associated glomerulonephritis (HBV-GN) and alleviating renal injury. Keywords: ferroptosis, hepatitis B virus associated glomerulonephritis, bone marrow mesenchymal stem cells, exosome, MIR-223-3pThis study investigates the protective mechanism of miR-223-3p in bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) against HBx-induced ferroptosis in renal podocytes. The research aims to understand how miR-223-3p targets HDAC2 to downregulate STAT3 phosphorylation, thereby alleviating podocyte injury. Key findings include: 1. **STAT3 Phosphorylation and Ferroptosis**: Inhibition of STAT3 phosphorylation significantly reduces HBx-induced ferroptosis in podocytes, as evidenced by improved cell viability, reduced lipid peroxidation, and decreased mitochondrial damage. 2. **HDAC2 and STAT3 Phosphorylation**: HDAC2 overexpression enhances STAT3 phosphorylation, promoting ferroptosis. In contrast, HDAC2 inhibition or miR-223-3p overexpression in BMSC-Exo reduces STAT3 phosphorylation and ameliorates ferroptosis. 3. **BMSC-Exo and Podocyte Protection**: BMSC-Exo carrying miR-223-3p effectively suppresses HDAC2 expression, leading to reduced HBx-induced ferroptosis in podocytes. This effect is mediated through the downregulation of STAT3 phosphorylation. 4. **Animal Model and In Vivo Validation**: In HBx transgenic mice, treatment with BMSC-Exo containing miR-223-3p significantly reduces renal damage, increases podocyte markers, and decreases ferroptosis-related markers. 5. **Conclusion**: The study demonstrates that BMSC-Exo-mediated delivery of miR-223-3p can effectively mitigate HBx-induced ferroptosis in podocytes, offering a novel therapeutic approach for treating hepatitis B virus-associated glomerulonephritis (HBV-GN) and alleviating renal injury. Keywords: ferroptosis, hepatitis B virus associated glomerulonephritis, bone marrow mesenchymal stem cells, exosome, MIR-223-3p