MiR‐155 promotes interleukin‐1β‐induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1‐mediated PI3K/Akt pathway
Autor: | Qiutong Li, Hongliang Zhang, Shentai Li, Zheng-liang Shi, Hua Zhang, Shu-xing Cao, Kai Deng, Zhi-yong Fan, Yinghui Liu |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Interleukin-1beta Chondrocyte miR-155 Phosphatidylinositol 3-Kinases 03 medical and health sciences Transduction (genetics) Chondrocytes 0302 clinical medicine PIK3R1 medicine Humans Cells Cultured PI3K/AKT/mTOR pathway Gene knockdown Chemistry Cartilage apoptosis Original Articles Cell Biology Extracellular Matrix Cell biology Class Ia Phosphatidylinositol 3-Kinase MicroRNAs osteoarthritis 030104 developmental biology medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis chondrocyte MiR‐155 Molecular Medicine Original Article Proto-Oncogene Proteins c-akt catabolic activity Signal Transduction |
Zdroj: | Journal of Cellular and Molecular Medicine |
ISSN: | 1582-4934 1582-1838 |
Popis: | Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation, in which elevated chondrocyte apoptosis and catabolic activity play an important role. MicroRNA‐155 (miR‐155) has recently been shown to regulate apoptosis and catabolic activity in some pathological circumstances, yet, whether and how miR‐155 is associated with OA pathology remain unexplored. We report here that miR‐155 level is significantly up‐regulated in human OA cartilage biopsies and also in primary chondrocytes stimulated by interleukin‐1β (IL‐1β), a pivotal pro‐catabolic factor promoting cartilage degradation. Moreover, miR‐155 inhibition attenuates and its overexpression promotes IL‐1β‐induced apoptosis and catabolic activity in chondrocytes in vitro. We also demonstrate that the PIK3R1 (p85α regulatory subunit of phosphoinositide 3‐kinase (PI3K)) is a target of miR‐155 in chondrocytes, and more importantly, PIK3R1 restoration abrogates miR‐155 effects on chondrocyte apoptosis and catabolic activity. Mechanistically, PIK3R1 positively regulates the transduction of PI3K/Akt pathway, and a specific Akt inhibitor reverses miR‐155 effects on promoting chondrocyte apoptosis and catabolic activity, phenocopying the results obtained via PIK3R1 knockdown, hence establishing that miR‐155 promotes chondrocyte apoptosis and catabolic activity through targeting PIK3R1‐mediated PI3K/Akt pathway activation. Altogether, our study discovers novel roles and mechanisms of miR‐155 in regulating chondrocyte apoptosis and catabolic activity, providing an implication for therapeutically intervening cartilage degradation and OA progression. |
Databáze: | OpenAIRE |
Externí odkaz: |