GPNMB在缺氧诱导的人绒毛膜滋养层细胞上皮-间质转化中的作用

doi:10.3969/j.issn.1006-5725.2025.20.001

Abstract

Abstract:

Objective To investigate the role of Glycoprotein non-metastatic melanoma protein B （GPNMB） in hypoxia-induced epithelial–mesenchymal transition （EMT） in human chorionic trophoblast HTR-8/SVneo cells. Methods HTR-8/SVneo cells were cultured in vitro to investigate the effect of hypoxia on GPNMB expression. The cells were transfected with either a GPNMB overexpression plasmid （pcDNA3.1-GPNMB）， small interfering RNA targeting GPNMB （si-GPNMB-1/2）， or their respective negative controls （pcDNA3.1-NC or si-NC）， and were also treated with the autophagy agonist rapamycin （Rap）. The experimental groups were categorized as follows： Normoxia， Hypoxia， Normoxia/Hypoxia + si-NC or si-GPNMB， Normoxia/Hypoxia + pcDNA3.1-NC or pcDNA3.1-GPNMB， Normoxia/Hypoxia + Rap， and Hypoxia + Rap + pcDNA3.1-NC or pcDNA3.1-GPNMB. GPNMB expression levels were evaluated using qRT-PCR， Western blotting， and immunofluorescence staining. The expression of autophagy-related proteins （LC3B Ⅱ/Ⅰ， p62） and epithelial-mesenchymal transition （EMT） markers （E-cadherin， N-cadherin） was analyzed by Western blotting. Cell migration and invasion capacities were assessed using wound healing and Transwell assays. Results Compared with the Normoxia group， the mRNA and protein levels of GPNMB were downregulated in the Hypoxia group. Additionally， the protein levels of p62 and N-cadherin were reduced， while LC3B Ⅱ/Ⅰ and E-cadherin expression levels were increased （P < 0.05）. Compared with the Hypoxia + si-NC group， the Hypoxia + si-GPNMB-2 group showed significantly decreased protein levels of p62 and N-cadherin， along with elevated levels of LC3B Ⅱ/Ⅰ and E-cadherin （P < 0.05）. Compared with the Hypoxia + pcDNA3.1-NC group， the Hypoxia + pcDNA3.1-GPNMB group exhibited opposite trends. Notably， compared with the Hypoxia group， the Hypoxia + Rap group showed increased LC3B Ⅱ/Ⅰ and E-cadherin levels， accompanied by reduced p62 and N-cadherin levels （P < 0.05）. However， compared with the Hypoxia + pcDNA3.1-GPNMB group， the Hypoxia + Rap + pcDNA3.1-GPNMB group attenuated the promoting effect of GPNMB overexpression on EMT in HTR-8/SVneo cells， as evidenced by decreased p62 and N-cadherin protein expression levels and increased LC3B Ⅱ/Ⅰ and E-cadherin protein expression levels （P < 0.05）. Conclusion In hypoxia-induced HTR-8/SVneo cells， GPNMB inhibits autophagy， promotes the epithelial-mesenchymal transition， and enhances cell migration and invasion.

Key words: glycoprotein nonmetastatic melanoma protein B, human chorionic trophoblast cells, autophagy, epithelial-mesenchymal transition, migration, invasion

CLC Number:

R714.25

Tian TIAN,Ping CAO,Xuhong ZHANG,Xiaohong MA,Jingrui LI,Xueqin DING,Xiaoming. YANG. The role of GPNMB in hypoxia induced epithelial-mesenchymal transition in human chorionic trophoblast cells[J]. The Journal of Practical Medicine, 2025, 41(20): 3135-3144.

Figures/Tables 7

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The role of GPNMB in hypoxia induced epithelial-mesenchymal transition in human chorionic trophoblast cells

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