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

Author:

Wang GuangORCID,Wang YongfengORCID,Li Jianglan,Peng Ruji,Liang Xinyin,Chen Xuedong,Jiang Guihua,Shi Jinfang,Si-ma Yanghu,Xu ShiqingORCID

Abstract

AbstractHyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC). It is often clinically complicated by malignant diseases or severe infections. Research on the molecular mechanism of High PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate, Bombyx mori, to investigate the effect of HPPC on circulating blood cells. We showed that HPPC affected blood cell homeostasis and enhanced blood cell phagocytosis, leading to increased reactive oxygen species levels, and induced programmed cell death that depended on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the JAK/STAT signaling pathway. Supplementation with endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Herein, we reported a novel signaling pathway by which HPPC affected blood cell homeostasis, which was different 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 monitoring index for hyperproteinemia.HighlightsHPPC induced proliferation of circulating blood cells through the JAK/STAT pathway, leading to a significant increase in the proportion of granulocytes.Supplementing endocrine hormone 20E improved hematopoietic function and restored the homeostasis of circulating blood cells through modulation of the JAK/STAT signaling pathway.HPPC induced PCD in blood cells through the endoplasmic reticulum-calcium ion release signaling pathway.Down-regulation of the gene expression of the hematopoietic factor Gcm could be used as a potential early monitoring index for hyperproteinemia.

Publisher

Cold Spring Harbor Laboratory

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