Immune thrombocytopenia induces autophagy and suppresses apoptosis in megakaryocytes

Abstract

Immune thrombocytopenia (ITP) is the main pathogenesis of excessive platelet destruction and abnormal megakaryocyte apoptosis, however, the mechanism underlying this abnormality in megakaryocytes remains to be elucidated. Since autophagy and apoptosis are closely interrelated, it can be speculated that the abnormal apoptosis of ITP megakaryocytes is associated with autophagy. To test this hypothesis, a total of 14 patients with ITP and 23 healthy controls were recruited. MEG‑01 cell line was cultured in vitro, and morphological changes were observed by light microscopy, apoptosis was evaluated by flow cytometric analysis of Annexin V‑FITC/propidium iodide staining and western blot analysis of B‑cell lymphoma (Bcl)‑2, Bcl‑associated X protein (Bax), Beclin‑1 and cleaved caspase 3. Apoptotic abnormalities and autophagy were observed in the ITP plasma group. Furthermore, Bax expression was downregulated, while Beclin‑1 was upregulated. Chloroquine can block autophagy induced by ITP and remove the ITP plasma inhibition of apoptosis. Therefore, it may be concluded that ITP may induce autophagy, the inhibition of which may be a novel treatment for ITP.

Abnormal expression of autophagy‐related proteins in immune thrombocytopenia

“…The data above collectively revealed an abnormal Beclin-1 immunoregulation; therefore, downregulating the expression of Beclin-1 in ITP patients might also represent a therapeutic approach against ITP. Liu et al found that ITP plasma induced inhibition of megakaryocyte apoptosis, resulting in decreased activation of caspase-3, leading to an increase in Beclin-1, 28 which verified our experimental results.…”

“…Studies found that ITP plasma induced autophagy and suppressed apoptosis in megakaryocytes. The inhibition of megakaryocyte apoptosis could result in impaired platelet release and reduced circulating platelets 28,38 …”

“…The inhibition of megakaryocyte apoptosis could result in impaired platelet release and reduced circulating platelets. 28,38 F I G U R E 4 Immunofluorescence analysis of Beclin-1 and SQSTM1/p62 (A) Average optical density of Beclin-1 was increased in active ITP patients compared with healthy controls (P> .05); (B) the double-positive rate of CD41 + Beclin-1 + was significantly increased in active ITP patients compared with healthy controls (P < .05); (C) the average optical density of p62 was significantly decreased in active ITP patients compared with healthy controls (P < .05); (D) the double-positive rate of CD41 + p62+ was significantly decreased in active ITP patients compared with healthy controls (P < .05). A P-value of less than 0.05 was considered statistically significant.…”

Megakaryocytic dysfunction in immune thrombocytopenia is linked to autophagy

“…This conclusion deserves further research. For example, current results need more case validation analyses, functional verification assays and larger population-based studies to confirm [103]. And this conclusion is in contrast to our treatment of ITP autophagy induced by rapamycin.…”

“…However, the study of Liu et al demonstrated that the plasma in ITP patients induces autophagy and suppresses apoptosis [103]. And the inhibition of autophagy may be a novel treatment in further investigation.…”