Sirolimus modulates the erythroid differentiation of K562 cells by upregulating SHP1

IF 2.4 3区医学 Q2 HEMATOLOGY

Annals of Hematology Pub Date : 2025-08-19 DOI:10.1007/s00277-025-06518-4

Yuan Yang, Zengwei Tang, Qinglin Hu, Chen Yang, Miao Chen, Hongmei Jing, Bing Han

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Abstract

Sirolimus is an effective treatment for acquired pure red cell aplasia (aPRCA), but the detail mechanism of sirolimus on red cell differentiation is incompletely understood. The aim of the study was to investigate whether sirolimus can induce the erythroid differentiation of K562 cells and investigate the potential regulation mechanism. Benzidine staining and flow cytometry were performed to determine the benzidine-/CD71-positive K562 cells with or without sirolimus treatment. The expression level of α-/ γ-globin in each group was determined by real-time qPCR, respectively. siRNA-targeted assays were performed to investigate the role of protein tyrosine phosphatase 1 (SHP1) in sirolimus-induced erythroid differentiation of K562 cells. The proportion of benzidine-staining/CD71-positive cells, and α- / γ-globin mRNA expression were increased in K562 cells treated with sirolimus. Sirolimus markedly inhibited mTOR and p-mTOR expression while upregulated SHP1 expression in K562 cells. Knockdown of SHP1 decrease α-/γ-globin mRNA level, CD71 protein expression levels and the proportion of benzidine-positive cells in the K562 cells. Additionally, knockdown of SHP1 can reverse the sirolimus-induced erythroid differentiation of K562 cells. Sirolimus treatment can promote the erythroid differentiation of K562 cells via upregulating of SHP1.

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西罗莫司通过上调SHP1调节K562细胞的红系分化。

西罗莫司是治疗获得性纯红细胞发育不全（aPRCA）的有效药物，但西罗莫司影响红细胞分化的具体机制尚不完全清楚。本研究旨在探讨西罗莫司是否能诱导K562细胞红系分化，并探讨其可能的调控机制。采用联苯胺染色和流式细胞术检测西罗莫司治疗前后K562细胞的联苯胺/ cd71阳性情况。实时荧光定量pcr检测各组α-/ γ-珠蛋白的表达水平。采用sirna靶向实验研究蛋白酪氨酸磷酸酶1 （SHP1）在西罗莫司诱导的K562细胞红系分化中的作用。西罗莫司处理后K562细胞中联苯胺染色/ cd71阳性细胞比例和α- / γ-珠蛋白mRNA表达增加。西罗莫司显著抑制K562细胞中mTOR和p-mTOR的表达，上调SHP1的表达。敲低SHP1可降低K562细胞中α-/γ-珠蛋白mRNA水平、CD71蛋白表达水平和联苯胺阳性细胞比例。此外，敲低SHP1可以逆转西罗莫司诱导的K562细胞红系分化。西罗莫司可通过上调SHP1促进K562细胞红系分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Hematology 医学-血液学

CiteScore

5.60

自引率

2.90%

发文量

304

审稿时长

2 months

期刊介绍： Annals of Hematology covers the whole spectrum of clinical and experimental hematology, hemostaseology, blood transfusion, and related aspects of medical oncology, including diagnosis and treatment of leukemias, lymphatic neoplasias and solid tumors, and transplantation of hematopoietic stem cells. Coverage includes general aspects of oncology, molecular biology and immunology as pertinent to problems of human blood disease. The journal is associated with the German Society for Hematology and Medical Oncology, and the Austrian Society for Hematology and Oncology.