Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling
| Autor: | Man-Seng Tam, Huige Hou, You-Jie Liu, Xiaofei Zheng, Huajun Wang, Lek-Hang Cheang, Ri-Wang Li, Zhao-Wen Xue, Jieruo Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
Histology QH301-705.5 Biophysics tendon stem cell Biology Article Rotator Cuff Injuries Rats Sprague-Dawley Tendons lncRNA microRNA medicine Gene silencing Animals Biology (General) miRNA Stem Cells Cell Differentiation Cell Biology musculoskeletal system Long non-coding RNA female genital diseases and pregnancy complications Tendon Cell biology Vascular endothelial growth factor A MicroRNAs medicine.anatomical_structure Mechanism of action embryonic structures RNA Long Noncoding medicine.symptom Stem cell Function (biology) Signal Transduction rotator cuff tear repair |
| Zdroj: | European Journal of Histochemistry, Vol 65, Iss 3 (2021) European Journal of Histochemistry : EJH |
| ISSN: | 2038-8306 |
| Popis: | Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury. |
| Databáze: | OpenAIRE |
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