Yu-Jiang Yang, Xin Zheng, Hai-Nan Lan
College of Animal Science and Technology, Jilin Agricultural University, Changchun, People's Republic of China.
Anim Cells Syst (Seoul). 2020 Apr 27;24(2):69-78. doi: 10.1080/19768354.2020.1735518. eCollection 2020.
Porcine growth hormone (pGH) is most important hormone which is involved in the growth and development of pig. However, a series of studies have indicated that neonatal pig is insensitive to pGH; the reason for this phenomenon is still not fully understood. In this work, we try to investigate this issue from the angle of intracellular signaling induced by pGH. In the present study, porcine hepatocytes from neonatal pig were used as a model, and confocal laser scanning microscopy (CLSM), Western blot, co-immunoprecipitation and colocalization assay were used to study pGH's signaling properties in hepatocytes of neonatal pig and explore the possible mechanism(s) for why intracellular signaling is insensitive to pGH. The results indicated that Janus kinase 2 and signal transducers and activators of transcription 5/3/1 (JAK2-STATs) signaling are not activated. We further investigated the possible mechanism(s) by which JAK2-STATs' signaling is not activated by pGH and growth hormone receptor (GHR) and found that the negative regulatory molecules of JAK2-STATs signaling may be associated with this phenomenon in the hepatocytes of neonatal pig. In addition, we also explored pGH's biology in hepatocytes from neonatal pig, it can be found that pGH/GHR could translocate into the cell nucleus, which implies that pGH/GHR may exhibit physiological roles based on their nuclear localization. We found that pGH could not trigger intracellular signaling in the hepatocytes of neonatal pigs, but not young pigs, which provides an important explanation for why the growth of neonatal pig is GH independent.
猪生长激素(pGH)是参与猪生长发育的最重要激素。然而,一系列研究表明新生仔猪对pGH不敏感;这一现象的原因仍未完全了解。在这项工作中,我们试图从pGH诱导的细胞内信号传导角度来研究这个问题。在本研究中,以新生仔猪的猪肝细胞为模型,利用共聚焦激光扫描显微镜(CLSM)、蛋白质免疫印迹法、免疫共沉淀和共定位分析来研究pGH在新生仔猪肝细胞中的信号特性,并探索细胞内信号对pGH不敏感的可能机制。结果表明,Janus激酶2和信号转导子及转录激活子5/3/1(JAK2-STATs)信号未被激活。我们进一步研究了pGH和生长激素受体(GHR)未激活JAK2-STATs信号的可能机制,发现JAK2-STATs信号的负调控分子可能与新生仔猪肝细胞中的这一现象有关。此外,我们还探索了pGH在新生仔猪肝细胞中的生物学特性,发现pGH/GHR可以转运到细胞核中,这意味着pGH/GHR可能基于其核定位发挥生理作用。我们发现pGH不能在新生仔猪而非幼龄仔猪的肝细胞中触发细胞内信号传导,这为新生仔猪生长为何不依赖生长激素提供了重要解释。