Department of Biochemistry, Inha University School of Medicine, Incheon 22212, Republic of Korea.
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea.
Int J Mol Sci. 2024 Mar 7;25(6):3092. doi: 10.3390/ijms25063092.
Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 () and sterol regulatory element binding protein () cleavage-activating protein () with increased expression of hepatocellular growth factor (), hepatocellular nuclear factor 4 alpha (), and albumin (). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.
非酒精性脂肪性肝病(NAFLD)已成为一种重要的肝脏疾病,其发病原因包括肥胖和糖尿病等因素。虽然目前正在研究针对 NAFLD 的治疗方法,但为了解决这一日益严重的健康问题,仍需要进一步的研究。NAFLD 的表现为肝脂肪变性,导致胰岛素抵抗和代谢综合征。本研究旨在验证嵌合成纤维细胞生长因子 21(FGF21)和肝细胞生长因子受体(HGFR)在 NAFLD 病变细胞中的再生潜力。本研究使用 AML12,一种鼠肝细胞系,来评估嵌合 FGF21/HGFR 表达的再生作用。通过过碘酸希夫(PAS)染色证实多糖积累,并用标记的 LDL 通过显微镜观察 LDL 摄取。通过 RT-PCR 进行的 mRNA 分析来分析 FGF21/HGFR 和 NAFLD 标志物的表达,结果显示乙酰辅酶 A 羧化酶 1()和固醇调节元件结合蛋白裂解激活蛋白()的表达减少,而肝细胞生长因子()、肝细胞核因子 4α()和白蛋白()的表达增加。这些发现证实了嵌合 FGF21/HGFR 在 AML12 细胞中的肝再生特性,为 NAFLD 的治疗探索开辟了新途径。