Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model

• DOI: 10.24272/j.issn.2095-8137.2021.397
• Publication Date: 2022-03-08T13:16:44Z
• Authors: Guang Wang; ; ; Yong-Feng Wang; Jiang-Lan Li; Ru-Ji Peng; Xin-Yin Liang; Xue-Dong Chen; Gui-Hua Jiang; Jin-Fang Shi; Yang-Hu Si-Ma; Shi-Qing Xu
• Keywords: Homeostasis; Janus kinase 2

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) scant. Here, an animal model of primary hyperproteinemia was constructed in invertebrate ( Bombyx mori) to investigate effects HPPC circulating blood cells. Results showed that affected cell homeostasis, leading reactive oxygen species levels, induced programmed death dependent endoplasmic reticulum-calcium ion signaling pathway. proliferation cells, mainly granulocytes, activating Janus kinase/signal transducer activator transcription (JAK/STAT) Supplementation endocrine hormone active substance 20E significantly reduced impact homeostasis. Thus, we identified novel pathway which affects differs from hyperglycemia, hyperlipidemia, hypercholesterolemia. In addition, down-regulation gene expression hematopoietic factor Gcm could be used as 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。.