Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and is often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate ( Bombyx mori) to investigate the effects of HPPC on circulating blood cells. Results showed that HPPC affected blood cell homeostasis, leading to increased reactive oxygen species levels, and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Supplementation with the endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Thus, we identified a novel signaling pathway by which HPPC affects blood cell homeostasis, which differs from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.
高蛋白血症是一种以血浆蛋白浓度（PPC）显著升高为指标的严重代谢紊乱疾病，临床常并发于多种恶性疾病或重度感染。然而，由于临床无法剥离原发性疾病的影响，目前对高PPC的分子机理研究甚少。该文在无脊椎模式动物家蚕中构建了一个原发性高蛋白血症动物模型，调查了高PPC对循环血细胞的影响。结果发现，高PPC严重影响血细胞稳态，导致活性氧水平升高，诱导了依赖内质网-钙离子信号途径的血细胞程序性死亡发生。另一方面，高PPC通过激活血细胞的JAK/STAT信号通路，诱导以颗粒细胞为主的血细胞增殖。补充内分泌激素活性物质20E治疗后，能够显著减轻高PPC对循环血细胞稳态的影响。因此，该文发现了一条高PPC影响血细胞稳态不同于高血糖、高血脂和高胆固醇的信号通路。此外发现，造血因子 Gcm的基因表达下调可作为潜在的高蛋白血症早期检测指标。.
Keywords: Animal model; Blood cell homeostasis; High plasma protein concentration (HPPC); JAK/STAT pathway; Programmed cell death.