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

• Published in: Dōngwùxué yánjiū Vol. 43; no. 3; pp. 301 - 318
• Main Authors: Wang, Guang, Wang, Yong-Feng, Li, Jiang-Lan, Peng, Ru-Ji, Liang, Xin-Yin, Chen, Xue-Dong, Jiang, Gui-Hua, Shi, Jin-Fang, Si-Ma, Yang-Hu, Xu, Shi-Qing
• Format: Journal Article
• Language: English
• Published: China Kunming Institute of Zoology, The Chinese Academy of Sciences 18.05.2022
• Subjects: Animal models; Animals; Antimicrobial agents; Apoptosis; Blood; Blood cells; Blood Cells - metabolism; Blood circulation; Calcium; Calcium (reticular); Calcium ions; Calcium signalling; Cell death; Cell proliferation; Disease; Disease Models, Animal; Endoplasmic reticulum; Gene expression; Granulocytes; Homeostasis; Hormones; Hypercholesterolemia; Hyperglycemia; Hyperlipidemia; Invertebrates; Janus kinase; Janus Kinases - genetics; Janus Kinases - metabolism; Kinases; Laboratory animals; Leukocytes (granulocytic); Medical prognosis; Metabolic disorders; Multiple myeloma; Neutrophils; Plasma; Proliferation; Proteins; Reactive oxygen species; Signal transduction; Signaling; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; Supplements; Transcription; Transducers; United States > US; China; Animal model; Programmed cell death; Blood cell homeostasis; JAK/STAT pathway; High plasma protein concentration (HPPC)
• ISSN: 2095-8137; 0254-5853
• DOI: 10.24272/j.issn.2095-8137.2021.397

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 ( ) 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 could be used as a potential early detection indicator for hyperproteinemia.