Sirolimus modulates the erythroid differentiation of K562 cells by upregulating SHP1.

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.