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lncRNA H19 sponging miR-93 to regulate inflammation in retinal epithelial cells under hyperglycemia via XBP1s

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Diabetic retinopathy (DR) is a major complication of both type 1 and type 2 diabetes. Recently, inflammation was found to play an important role in DR pathogenesis. But the mechanism has not been fully understood.


ARPE-19 cells were cultured under normal condition and high-glucose condition, then the expressions of miR-93, XBP1s and lncRNA H19 were measured using RT-qPCR or western blots. Besides, the mRNA level of eIF2α and GRP78 and protein level of p-eIF2α and GRP78 were measured by RT-qPCR or western blots. In addition, RT-qPCR and ELISA were adopted to examine the expression and secretion of cytokine factors in these conditions. Dual-luciferase reporter gene assay was used to elucidate the binding and regulation among XBP1s, miR-93 and H19. RNA immunoprecipitation was also performed to verify the interaction between H19 and miR-93. The expressions of DNAJC3 and DNAJB9, the downstream targets of XBP1s, were detected by RT-qPCR.


We identified that H19 and XBP1s were down-regulated in ARPE-19 cells under high-glucose condition, while miR-93 was up-regulated. ER stress inducers TM and IRE1 inhibitor STF-083010 were adopted and data suggest that ER stress could be induced during high-glucose treatment. In addition, the altered expressions of miR-93, XBP1s and H19 might mediate the increased level of pro-inflammatory cytokines. Furthermore, miR-93 interacted with either lncRNA H19 or XBP1s then modulating the inflammatory processes.


H19 played an important role in regulating inflammatory processes in retinal endothelial cells under high-glucose condition through modulating miR-93/XBP1s axis.

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Availability of data and material

All data generated or analyzed during this study are included in this published article.



Diabetic retinopathy




Spliced X-box-binding protein 1


Long non-coding RNA


Quantitative polymerase chain reaction


Enzyme-linked immunosorbent assays


Endoplasmic reticulum


Tumor necrosis factor-α


Vascular endothelial growth factor


Retinal endothelial cells


Myocardial infarction-associated transcript


Antisense RNA to INK4 locus


RNA-binding protein immunoprecipitation




Unfolded protein response


Inositol-requiring protein-1α


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Correspondence to Rong Luo.

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Luo, R., Xiao, F., Wang, P. et al. lncRNA H19 sponging miR-93 to regulate inflammation in retinal epithelial cells under hyperglycemia via XBP1s. Inflamm. Res. 69, 255–265 (2020). https://doi.org/10.1007/s00011-019-01312-1

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  • Long non-coding RNA
  • H19
  • MicroRNA
  • miR-93
  • Diabetic retinopathy
  • Inflammation