PEDF reduces malignant cells proliferation and inhibits the progression of myelofibrosis in myeloproliferative neoplasms

Yanjie Li; Hui Gao; Hongyan Dong; Weiwei Wang; Zhengqing Xu; Guozhang Wang; Yahui Liu; Haiyang Wang; Wen Ju; Jianlin Qiao; Kailin Xu; Chunling Fu; Lingyu Zeng

doi:10.1016/j.bcp.2022.115013

PEDF reduces malignant cells proliferation and inhibits the progression of myelofibrosis in myeloproliferative neoplasms

Biochem Pharmacol. 2022 May:199:115013. doi: 10.1016/j.bcp.2022.115013. Epub 2022 Mar 19.

Authors

Yanjie Li¹, Hui Gao¹, Hongyan Dong², Weiwei Wang¹, Zhengqing Xu¹, Guozhang Wang¹, Yahui Liu¹, Haiyang Wang³, Wen Ju¹, Jianlin Qiao¹, Kailin Xu⁴, Chunling Fu⁵, Lingyu Zeng⁶

Affiliations

¹ Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
² Xuzhou Medical University, Xuzhou, China.
³ Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁴ Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China; Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
⁵ Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China. Electronic address: fucl@xzhmu.edu.cn.
⁶ Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China; College of Medical Technology, Xuzhou Medical University, Xuzhou, China. Electronic address: zengly2000@xzhmu.edu.cn.

PMID: 35318038
DOI: 10.1016/j.bcp.2022.115013

Abstract

Pigment epithelial-derived factor (PEDF) exerts a broad spectrum of activities and has been implicated in diverse biological processes and a variety of diseases. However, the role of PEDF in myeloproliferative neoplasms (MPN) remains unknown. In this study, we found that PEDF expression was down-regulated in MPN patients and MPL^W515L-transuduced mice. Exogenous PEDF inhibited the peripheral blood cell proliferation in MPL^W515L-transuduced mice, reduced tumor cells in bone marrow and spleen, ameliorated hepatosplenomegaly, reduced extramedullary hemopoiesis in the spleen, and prolonged the overall survival of MPN mice. More importantly, PEDF inhibited the progression of myelofibrosis. Moreover, PEDF significantly reduced the proliferation of MPN cells in vitro, especially megakaryocyte-biased HSCs. Furthermore, PEDF induced the apoptosis of MPN cells and reduced the secretion of TGF-β1 in cell culture supernatant. Exogenous PEDF inhibits the proliferation of MPN cells and the progression of myelofibrosis, indicating that it might play an anti-tumor and anti-fibrotic role in MPN. This study implies that PEDF might be a novel agent for the treatment of MPN.

Keywords: Malignant cells; Myelofibrosis; Myeloproliferative neoplasms; PEDF; TGF-β.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation
Humans
Megakaryocytes
Mice
Myeloproliferative Disorders* / pathology
Neoplasms*
Primary Myelofibrosis* / drug therapy
Primary Myelofibrosis* / pathology