Posttranscriptional regulation of MMP‐9 by HuR contributes to IL‐1β‐induced pterygium fibroblast migration and invasion
2019
Inflammation is considered to be critical in the pterygium progression and recurrence. However, the underlying molecular mechanism is not well understood. Herein, we investigated the potential role of RNA binding protein human antigen R (HuR) responsible for the impact of inflammation on pterygium development. The expression of HuR and matrix metallopeptidase-9 (MMP-9) in pterygium and normal conjunctiva was detected with immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The influence of interleukin-1beta (IL-1beta) on HuR expression and cellular distribution was determined with western blot and immunofluorescence. The pterygium fibroblast (PTF) migration was determined with scratch wound healing assay and Transwell migration assay. MMP-9 production was determined with qRT-PCR and gelatin zymography. The interaction between HuR and MMP-9 was investigated with RNP immunoprecipitation (IP) followed by RT-PCR and messenger RNA (mRNA) stability analysis. HuR and MMP-9 expression are elevated in pterygium, especially progressive pterygium compared with normal conjunctiva. IL-1beta could increase the expression and nucleus-cytoplasm shuttle of HuR in cultured PTFs. HuR mediated the stimulatory effect of IL-1beta on PTF migration and MMP-9 production. HuR bound to MMP-9 mRNA and in turn increased it stability. Our results suggest that posttranscriptional regulation of MMP-9 via stabilizing mRNA by HuR might contribute to the stimulatory effect of inflammatory factor IL-1beta on pterygium progression. These findings shed light on the pathogenesis of pterygium and provide a promising target for adjuvant treatment of pterygium.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
49
References
4
Citations
NaN
KQI