四个半 LIM 结构域蛋白 2（FHL2）缺乏会加重小鼠肝纤维化。

BACKGROUND

Four and one half LIM domain protein 2 (FHL2) has been reported to be a key regulator in many cellular processes being associated with fibrogenesis such as cell migration and contraction. Moreover, hepatic FHL2 is involved in regulation pathways mediating proliferation and cell death machineries. We here investigated the role of FHL2 in the setting of experimental and clinical liver fibrosis.

METHODS

FHL2(-/-) and wild type (wt) mice were challenged with CCl(4). Fibrotic response was assessed by quantitative real time PCR (qRT-PCR) of fibrotic marker genes, measurement of hydroxyproline content and histological methods. Murine FHL2(-/-) and hepatic stellate cells (HSC) were isolated and investigated via immunofluorescence. Human fibrotic and normal liver samples were analysed immunohistochemically using antibodies directed against FHL2.

RESULTS

FHL2(-/-) mice displayed aggravated liver fibrosis compared to wt mice. However, immunofluorescence revealed no significant morphological changes in cultured FHL2(-/-) and wt myofibroblasts (MFB). In human liver samples, FHL2 was strongly expressed both in the nucleus and cytoplasm in MFB of fibrotic livers. In contrast, FHL2 expression was absent in normal liver tissue.

CONCLUSIONS

Deficiency of FHL2 results in aggravation of murine liver fibrosis. In human liver samples, FHL2 is expressed in activated HSCs and portal fibroblasts in human fibrotic livers, pointing to a central role of FHL2 for human hepatic fibrogenesis as well.

背景

四个和一个半 LIM 结构域蛋白 2（FHL2）已被报道为许多细胞过程的关键调节剂，与纤维化有关，如细胞迁移和收缩。此外，肝 FHL2 参与调节增殖和细胞死亡机制的途径。我们在此研究了 FHL2 在实验性和临床肝纤维化中的作用。

方法

用 CCl4 挑战 FHL2(-/-)和野生型（wt）小鼠。通过纤维化标记基因的定量实时 PCR（qRT-PCR）、羟脯氨酸含量测定和组织学方法评估纤维化反应。分离和研究了小鼠 FHL2(-/-)和肝星状细胞（HSC），并通过免疫荧光进行了研究。使用针对 FHL2 的抗体，对人纤维化和正常肝组织进行免疫组织化学分析。