Regulation of Cytokine Signaling Pathways in the Eye

细胞因子信号转导抑制因子（SOCS）是一类通过酪氨酸激酶和JAK/STAT信号转导途径进行信号转导的细胞因子诱导型反馈调节因子。到目前为止，已经描述了6个不同的成员，并且根据组织，不同的SOCS响应于特定的细胞因子或生长因子而被激活。参与透镜生长和分化的几种细胞因子（PDGF、EGF、IGF）激活JAK激酶和STAT途径。然而，关闭这些细胞因子传递的信号的调节机制是未知的。我们通过Western blotting和RT-PCR分析确定SOCS和STAT基因是否在大鼠和小鼠晶状体中组成性和诱导性表达，以及一些充分表征的透镜上皮细胞系。培养的透镜细胞也用PDGF、EGF或IGF处理，以表征由这些生长因子在透镜细胞中诱导的SOCS基因库。 通过DNA序列分析验证了SOCS转录本的真实性。检测到所有已知STAT的表达，但STAT 2和STAT 4除外。在鼠透镜和透镜细胞系中也检测到大多数SOCS成员（SOCS 1除外）的组成型表达。我们的数据表明，SOCS蛋白可能在关闭眼透镜中的JAK/STAT信号中发挥重要作用。进一步表征透镜SOCS蛋白可能提供有价值的洞察这些细胞因子信号传导的负调节因子在透镜和眼睛发育中的作用。

Suppressors of cytokine signaling (SOCS) are a family of inducible feed-back regulators of cytokines that signal through tyrosine kinases and the JAK/STAT signaling pathway. Thus far 6 distinct members have been described and depending on the tissue, different SOCS are activated in response to particular cytokines or growth factors. Several cytokines (PDGF, EGF, IGF) implicated in lens growth and differentiation activate JAK kinases and STAT pathways. However, regulatory mechanisms that switch-off signals transmitted by these cytokines are unknown. We determined by Western blotting and RT-PCR analyses whether SOCS and STAT genes are constitutively and inducibly expressed in rat and mouse lenses, as well as, some well characterized lens epithelial cell lines. Cultured lens cells were also treated with either PDGF, EGF or IGF to characterize the repertoire of SOCS genes induced in lens cells by these growth factors. Authenticity of the SOCS transcripts was verified by DNA sequence analysis. Expression of all known STATs, with exception STAT2 and STAT4 was detected. Constitutive expression of most SOCS members (except SOCS1) was also detected in the murine lens and lens cell lines. Our data suggest that SOCS proteins may play significant roles in switching-off JAK/STAT signals in the ocular lens. Further characterization of lens SOCS proteins may provide valuable insight into the role of these negative regulators of cytokine signaling in lens and eye development.