Abstract
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.
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This study was supported by grants from the National Natural Science Youth Foundation of China (Grant no. 81700905) and Funds from Scientific Studies of Higher Education Institution in Henan (Grant no. 18A3210015) and Youth Funds from the First Affiliated Hospital of Zhengzhou University.
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Zhang, J., Fan, W., Neng, L. et al. 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. Human Cell 34, 1093–1102 (2021). https://doi.org/10.1007/s13577-021-00521-3
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DOI: https://doi.org/10.1007/s13577-021-00521-3