Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Huang Q, Tang J. Age-related hearing loss or presbycusis. Eur Arch Oto-rhino-laryngol. 2010;267(268):1179–91. https://doi.org/10.1007/s00405-010-1270-7.

    Article  Google Scholar 

  2. Gopinath B, Rochtchina E, Wang JJ, Schneider J, Leeder SR, Mitchell P. Prevalence of age-related hearing loss in older adults: Blue Mountains Study. Arch Intern Med. 2009;169(4):415–6. https://doi.org/10.1001/archinternmed.2008.597.

    Article  PubMed  Google Scholar 

  3. Cohen-Salmon M, Regnault B, Cayet N, Caille D, Demuth K, Hardelin JP, et al. Connexin30 deficiency causes intrastrial fluid-blood barrier disruption within the cochlear stria vascularis. Proc Natl Acad Sci USA. 2007;104(15):6229–34. https://doi.org/10.1073/pnas.0605108104.

    Article  CAS  PubMed  Google Scholar 

  4. Zhang F, Dai M, Neng L, Zhang JH, Zhi Z, Fridberger A, et al. Perivascular macrophage-like melanocyte responsiveness to acoustic trauma—a salient feature of strial barrier associated hearing loss. FASEB J. 2013;27(9):3730–40. https://doi.org/10.1096/fj.13-232892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhang W, Dai M, Fridberger A, Hassan A, Degagne J, Neng L, et al. Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid-blood barrier. Proc Natl Acad Sci USA. 2012;109(26):10388–93. https://doi.org/10.1073/pnas.1205210109.

    Article  PubMed  Google Scholar 

  6. Su Z, Xiong H, Pang J, Lin H, Lai L, Zhang H, et al. LncRNA AW112010 promotes mitochondrial biogenesis and hair cell survival: implications for age-related hearing loss. Oxid Med Cell Longev. 2019;2019:6150148. https://doi.org/10.1155/2019/6150148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liang C, Zhao T, Li H, He F, Zhao X, Zhang Y, et al. Long non-coding RNA ITIH4-AS1 accelerates the proliferation and metastasis of colorectal cancer by activating JAK/STAT3 signaling. Mol Ther Nucleic Acids. 2019;18:183–93. https://doi.org/10.1016/j.omtn.2019.08.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yin J, Park G, Kim TH, Hong JH, Kim YJ, Jin X, et al. Pigment epithelium-derived factor (PEDF) expression induced by EGFRvIII promotes self-renewal and tumor progression of glioma stem cells. PLoS Biol. 2015;13(5):e1002152. https://doi.org/10.1371/journal.pbio.1002152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Keithley EM, Canto C, Zheng QY, Fischel-Ghodsian N, Johnson KR. Age-related hearing loss and the ahl locus in mice. Hear Res. 2004;188(1–2):21–8. https://doi.org/10.1016/s0378-5955(03)00365-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhao T, Liu X, Sun Z, Zhang J, Zhang X, Wang C, et al. RNA-seq analysis of potential lncRNAs for age-related hearing loss in a mouse model. Aging. 2020;12(8):7491–510. https://doi.org/10.18632/aging.103103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hao S, Wang L, Zhao K, Zhu X, Ye F. Rs1894720 polymorphism in MIAT increased susceptibility to age-related hearing loss by modulating the activation of miR-29b/SIRT1/PGC-1α signaling. J Cell Biochem. 2019;120(4):4975–86. https://doi.org/10.1002/jcb.27773.

    Article  CAS  PubMed  Google Scholar 

  12. Yao P, Li YL, Chen Y, Shen W, Wu KY, Xu WH. Overexpression of long non-coding RNA Rian attenuates cell apoptosis from cerebral ischemia–reperfusion injury via Rian/miR-144-3p/GATA3 signaling. Gene. 2020;737:144411. https://doi.org/10.1016/j.gene.2020.144411.

    Article  CAS  PubMed  Google Scholar 

  13. Bijkerk R, Au YW, Stam W, Duijs JMGJ, Koudijs A, Lievers E, et al. Long non-coding RNAs Rian and Miat mediate myofibroblast formation in kidney fibrosis. Front Pharmacol. 2019;10:215. https://doi.org/10.3389/fphar.2019.00215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Neng L, Zhang W, Hassan A, Zemla M, Kachelmeier A, Fridberger A, et al. Isolation and culture of endothelial cells, pericytes and perivascular resident macrophage-like melanocytes from the young mouse ear. Nat Protoc. 2013;8(4):709–20. https://doi.org/10.1038/nprot.2013.033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang F, Zhang J, Neng L, Shi X. Characterization and inflammatory response of perivascular-resident macrophage-like melanocytes in the vestibular system. J Assoc Res Otolaryngol. 2013;14(5):635–43. https://doi.org/10.1007/s10162-013-0403-2.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Neng L, Zhang J, Yang J, Zhang F, Lopez IA, Dong M, et al. Structural changes in the strial blood-labyrinth barrier of aged C57BL/6 mice. Cell Tissue Res. 2015;361(3):685–96. https://doi.org/10.1007/s00441-015-2147-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang J, Chen S, Hou Z, Cai J, Dong M, Shi X. Lipopolysaccharide-induced middle ear inflammation disrupts the cochlear intra-strial fluid-blood barrier through down-regulation of tight junction proteins. PLoS ONE. 2015;10(3):e0122572. https://doi.org/10.1371/journal.pone.0122572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, No 1 Jianshe Road, Zhengzhou, 450052, China

    Jinhui Zhang, Wenya Fan, Lingling Neng, Bei Chen, Bin Zuo & Wei Lu

Authors
  1. Jinhui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenya Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lingling Neng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bin Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jinhui Zhang or Wei Lu.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (TIF 67 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-021-00521-3

Keywords

Search

Navigation