Effects of leptin-modified human placenta-derived mesenchymal stem cells on angiogenic potential and peripheral inflammation of human umbilical vein endothelial cells (HUVECs) after X-ray radiation.

Shu Chen; Qian Wang; Bing Han; Jia WU; Ding-kun Liu; Jun-dong Zou; Mi Wang; Zhi-hui Liu

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Effects of leptin-modified human placenta-derived mesenchymal stem cells on angiogenic potential and peripheral inflammation of human umbilical vein endothelial cells (HUVECs) after X-ray radiation.

Author: Shu CHEN ¹ ; Qian WANG ² ; Bing HAN ³ ; Jia WU ² ; Ding-Kun LIU ² ; Jun-Dong ZOU ² ; Mi WANG ² ; Zhi-Hui LIU ²
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1. Department of Thoracic Surgery, the Second Hospital of Jilin University, Changchun 130041, China.
2. Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun 130021, China.
3. Department of Radiology, the Second Hospital of Jilin University, Changchun 130041, China.
Publication Type:Journal Article
Keywords: Leptin; Angiogenesis; Pro-inflammatory cytokines; X-ray radiation; Human placenta-derived mesenchymal stem cells (HPMSCs); Human umbilical vein endothelial cells (HUVECs)
MeSH: Cell Proliferation; Cells, Cultured; Cytokines/biosynthesis*; Female; Human Umbilical Vein Endothelial Cells/radiation effects*; Humans; Inflammation/etiology*; Leptin/pharmacology*; Mesenchymal Stem Cells/physiology*; Neovascularization, Physiologic/physiology*; Placenta/cytology*; Pregnancy; STAT3 Transcription Factor/genetics*; Transcription Factor RelA/genetics*; X-Rays
From: Journal of Zhejiang University. Science. B 2020;21(4):327-340
CountryChina
Language:English
Abstract: Combined radiation-wound injury (CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells (HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells (HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. The secretion of pro-inflammatory cytokines (human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay (ELISA). The expression of pro-angiogenic factors (vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)) mRNA was detected by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Relevant molecules of the nuclear factor-κB (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs (HPMSCs/ leptin) exhibited better cell proliferation, migration, and angiogenic potential (expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines (human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.