细胞因子诱导的含 SH2 结构域蛋白（CISH）在红细胞生成中的调节作用。

Role of Cytokine-Inducible SH2 Domain-Containing (CISH) Protein in the Regulation of Erythropoiesis.

机构信息

School of Medicine, Deakin University, Waurn Ponds, Geelong, VIC 3216, Australia.

College of Science, University of Baghdad, Baghdad 10071, Iraq.

出版信息

Biomolecules. 2023 Oct 12;13(10):1510. doi: 10.3390/biom13101510.

DOI:10.3390/biom13101510

PMID:37892192

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10604548/

Abstract

The cytokine-inducible SH2 domain-containing (CISH) protein was the first member of the suppressor of cytokine signaling (SOCS) family of negative feedback regulators discovered, being identified in vitro as an inducible inhibitor of erythropoietin (EPO) signaling. However, understanding of the physiological role played by CISH in erythropoiesis has remained limited. To directly assess the function of CISH in this context, mice deficient in CISH were characterized with respect to developmental, steady-state, and EPO-induced erythropoiesis. was strongly expressed in the fetal liver, but CISH knockout (KO) mice showed only minor disruption of primitive erythropoiesis. However, adults exhibited mild macrocytic anemia coincident with subtle perturbation particularly of bone marrow erythropoiesis, with EPO-induced erythropoiesis blunted in the bone marrow of KO mice but enhanced in the spleen. was expressed basally in the bone marrow with induction following EPO stimulation in bone marrow and spleen. Overall, this study indicates that CISH participates in the control of both basal and EPO-induced erythropoiesis in vivo.

摘要

细胞因子诱导的含 SH2 结构域蛋白（CISH）是第一个被发现的细胞因子信号转导抑制因子（SOCS）家族负反馈调节剂成员，它在体外被鉴定为红细胞生成素（EPO）信号的诱导抑制剂。然而，CISH 在红细胞生成中的生理作用仍然知之甚少。为了直接评估 CISH 在这种情况下的功能，我们对 CISH 缺陷小鼠进行了发育、稳态和 EPO 诱导的红细胞生成特征描述。CISH 在胎儿肝脏中强烈表达，但 CISH 敲除（KO）小鼠仅表现出轻微的原始红细胞生成障碍。然而，成年人表现出轻微的巨红细胞性贫血，同时骨髓红细胞生成受到微妙的干扰，EPO 诱导的骨髓红细胞生成在 KO 小鼠中减弱，而在脾脏中增强。CISH 在骨髓中基础表达，在骨髓和脾脏中 EPO 刺激后诱导表达。总的来说，这项研究表明 CISH 参与体内基础和 EPO 诱导的红细胞生成的控制。