Posttranscriptional regulation of MMP‐9 by HuR contributes to IL‐1β‐induced pterygium fibroblast migration and invasion
| Autor: | Qing-Yang Feng, Zi-Xuan Hu, Hong-Yang Li, Hong-Wei Pan, Mei-Jun Li, Yu-Hong Cui, Wen-Lin Zheng, Xi-Ling Song, Zhi-Yi Xu, Jia-Hui Li, Zhi-Jie Li, Qun Liu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Physiology RNA Stability Interleukin-1beta Clinical Biochemistry RNA-binding protein Matrix metalloproteinase Pterygium ELAV-Like Protein 1 Fibroblast migration 03 medical and health sciences 0302 clinical medicine Western blot Cell Movement medicine Humans Fibroblast Aged Inflammation Messenger RNA Pterygium (conjunctiva) medicine.diagnostic_test Chemistry Cell Biology Fibroblasts Middle Aged medicine.disease eye diseases Reverse transcription polymerase chain reaction 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Matrix Metalloproteinase 9 030220 oncology & carcinogenesis Disease Progression Cancer research Female sense organs Conjunctiva Protein Processing Post-Translational |
| Zdroj: | Journal of Cellular Physiology. 235:5130-5140 |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | 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-1β (IL-1β) 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-1β could increase the expression and nucleus-cytoplasm shuttle of HuR in cultured PTFs. HuR mediated the stimulatory effect of IL-1β 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-1β on pterygium progression. These findings shed light on the pathogenesis of pterygium and provide a promising target for adjuvant treatment of pterygium. |
| Databáze: | OpenAIRE |
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