Long non-coding RNA Rian promotes the expression of tight junction proteins in endothelial cells by regulating perivascular-resident macrophage-like melanocytes and PEDF secretion

Perivascular-resident macrophage-like melanocytes (PVM/Ms) can upregulate the expression of tight junction-related proteins in endothelial cells (ECs) by secreting pigment epithelial-derived factor (PEDF), and thereby regulate the permeability of the intrastrial fluid–blood barrier critical for main...

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Published in:Human cell : official journal of Human Cell Research Society 2021-07, Vol.34 (4), p.1093-1102
Main Authors: Zhang, Jinhui, Fan, Wenya, Neng, Lingling, Chen, Bei, Zuo, Bin, Lu, Wei
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - genetics
Biomedical and Life Sciences
Cell Biology
Cell culture
Cell Survival - genetics
Cell viability
Cells, Cultured
Cochlea
Cochlea - metabolism
Endothelial cells
Endothelial Cells - metabolism
Eye Proteins - genetics
Eye Proteins - metabolism
Gene Expression - genetics
Gynecology
Homeostasis
Hypoxia
Inner ear
Life Sciences
Macrophages
Melanocytes
Melanocytes - physiology
Mice
Mice, Inbred C57BL
Nerve Growth Factors - genetics
Nerve Growth Factors - metabolism
Non-coding RNA
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Nuclear Proteins - physiology
Nuclear transport
Oncology
Permeability
Protein Binding - genetics
Proteins
Reproductive Medicine
Research Article
RNA, Long Noncoding - physiology
RNA-Binding Protein FUS - metabolism
Secretion
Serpins - genetics
Serpins - metabolism
Stat3 protein
STAT3 Transcription Factor - metabolism
Stem Cells
Surgery
Tight Junction Proteins - genetics
Tight Junction Proteins - metabolism
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Summary:Perivascular-resident macrophage-like melanocytes (PVM/Ms) can upregulate the expression of tight junction-related proteins in endothelial cells (ECs) by secreting pigment epithelial-derived factor (PEDF), and thereby regulate the permeability of the intrastrial fluid–blood barrier critical for maintaining inner ear homeostasis. This study aimed to investigate the effects of long non-coding RNA (lncRNA) Rian on cell growth of PVM/Ms and PVM/Ms regulation of intrastrial fluid–blood barrier integrity mediated by PEDF. Rian was downregulated in the aged cochlea from 12-month-old C57BL/6 mice. Rian overexpression inhibited cell apoptosis and promoted cell viability of hypoxia-injured PVM/Ms as well as increased the concentration and expression of PEDF secreted by PVM/Ms. In contrast, Rian silencing exerted the opposite effects. Furthermore, in a cell co-culture model of ECs and PVM/Ms, Rian overexpression in PVM/Ms increased the expression of the junction-associated proteins in co-cultured ECs, and this effect was abrogated by blockade of PEDF by anti-PEDF in PVM/Ms. Further mechanistical investigation revealed that Rian promoted STAT3 nuclear translocation and activation by binding to FUS, and thereby promoted the secretion of PEDF. Collectively, Rian attenuates PVM/Ms injury and strengthens the ability of PVM/Ms to maintain the integrity of the endothelial barrier by promoting PEDF expression.
ISSN:1749-0774
0914-7470
1749-0774
DOI:10.1007/s13577-021-00521-3