cBleomycin restricts the glycolysis of lymphatic endothelial cells by inhibiting dimeric PKM2 formation: A novel mechanism for lymphatic malformation treatment.
Biochemical pharmacology(2022)
Abstract
Glycolysis is activated in lymphatic endothelial cells and contributes to the development of lymphatic malformations (LMs). Bleomycin (BLM) is the most wildly used sclerosant for LMs, but its mechanisms are unknown. Here, our data showed that BLM suppressed the glycolysis of human dermal lymphatic endothelial cells (HDLECs) via inhibiting the expression and nucleus translocation of pyruvate kinase M2 isoform (PKM2) and inhibited dimeric PKM2 formation. Furthermore, the proliferation of LM lesions was inhibited by BLM through the down-regulation of nuclear PKM2 in the rat model. Additionally, PKM2, especially the nuclear PKM2 along with Ki-67, was inhibited in the lymphatic vessels of BLM-treated LMs. Our findings provide a new molecular mechanism of BLM in LM sclerotherapy treatment.
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Key words
Bleomycin,Glycolysis,Lymphatic malformations,PKM2
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