Quantitative LC\u2013MS/MS uncovers the regulatory role of autophagy in immune thrombocytopenia

Rui-Jie Sun,Ning-Ning Shan,Shu-Yan Liu,Jing-Jing Zhu,Dong-Mei Yin,Dai Yuan

doi:10.1186/s12935-021-02249-4

Abstract

BackgroundImmune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease whose pathogenesis is associated with bone marrow megakaryocyte maturation disorder and destruction of the haematopoietic stem cell microenvironment.MethodsIn this study, we report the qualitative and quantitative profiles of the ITP proteome. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was conducted to elucidate the protein profiles of clinical bone marrow mononuclear cell (BMMC) samples from ITP patients and healthy donors (controls). Gene Ontology (GO) and Kyoto Encyclopaedia Genes and Genome (KEGG) pathway analyses were performed to annotate the differentially expressed proteins. A protein–protein interaction (PPI) network was constructed with the BLAST online database. Target proteins associated with autophagy were quantitatively identified by parallel reaction monitoring (PRM) analysis.ResultsOur approaches showed that the differentially expressed autophagy-related proteins, namely, HSPA8, PARK7, YWHAH, ITGB3 and CSF1R, were changed the most. The protein expression of CSF1R in ITP patients was higher than that in controls, while other autophagy-related proteins were expressed at lower levels in ITP patients than in controls.ConclusionBioinformatics analysis indicated that disruption of the autophagy pathway is a potential pathological mechanism of ITP. These results can provide a new direction for exploring the molecular mechanism of ITP.

Highlights

Immune thrombocytopenia (ITP) is a multifactorial bleeding disease characterized by a breakdown of immune tolerance leading to a platelet count decline
Using the networkD3 R package, we revealed some highly connected subnetworks among autophagy proteins, including heat shock protein family A (Hsp70) member 8 (HSPA8), Parkinson’s disease 7 (PARK7), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide, isoform CRA_b (YWHAH), integrin beta-3 (ITGB3) and colony-stimulating factor 1 receptor (CSF1R)
The expression of the CSF1R protein in ITP patients was higher than that in controls, while the other autophagy-related proteins were expressed at lower levels in ITP patients than in controls

Summary

Introduction

Immune thrombocytopenia (ITP) is a multifactorial bleeding disease characterized by a breakdown of immune tolerance leading to a platelet count decline. Bone marrow fluid is a vital bodily tissue that has been extensively studied to elucidate the physiology and pathology of the haematological system. Autophagy is involved in cell development, intracellular quality control, adaptation, starvation, ageing, tumour suppression, innate immunity, and other processes [5]. Autophagy plays an important role in maintaining the microenvironment and stemness of haematopoietic stem cells [5] and in regulating megakaryopoiesis and platelet function [6]. Immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease whose pathogenesis is associated with bone marrow megakaryocyte maturation disorder and destruction of the haematopoietic stem cell microenvironment

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Results

Conclusion