Hypoxia-induced microRNA-146a represses Bcl-2 through Traf6/IRAK1 but not Smad4 to promote chondrocyte autophagy
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Guanghui Chen
, Xin Gao , Jing Wang , Cheng Yang , Yang Wang , Yonggang Liu , Weiwei Zouand Tielong Liu
Abstract
It has been shown that hypoxia stimulation promotes chondrocytes autophagy partly through HIF-1α, miR-146a and Bcl-2 progressively, and this mechanism represented the connection among hypoxia, miR-146a and autophagy, and provides a possible therapeutic strategy for osteoarthritis. However, the interaction between miR-146a and Bcl-2 is still unclear. Here in a hypoxic environment, we quantified the three reported miR-146a targets: two inflammation related targets Traf6, IRAK1; and the only reported target in chondrocytes Smad4. We confirmed the regulative function of miR-146a between hypoxia and these genes, and explored the Bcl-2 expression and autophagy level under extrinsic up-regulation of these three gene separately. All the three genes were down-regulated by hypoxia. Surprisingly, Traf6 and IRAK, but not the unique Smad4 in chondrocytes, were restored by antagomiR-146a. Both Ad-Traf6 and Ad-IRAK1 reinstated hypoxia or miR-146a repressed Bcl-2. However, Ad-Smad4 did not affect Bcl-2 in hypoxia or normoxia. The autophagy level showed a reverse variability compared to Bcl-2. Taken together, our results provided evidence that Smad4, the unique reported target for miR-146a in chondrocytes is unusually not involved in the chondrocytes autophagy, while the Traf6 and IRAK1 are the new targets for miR-146a in chondrocytes during autophagy.
Funding source: National Natural Science Foundation of China
Award Identifier / Grant number: 81372874
Funding statement: This work was supported by the National Natural Science Foundation of China (Grant 81372874).
Acknowledgements
This work was supported by the National Natural Science Foundation of China (Grant 81372874).
Conflict of interest statement: The authors indicate no potential conflicts of interest.
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©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
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- The role of whey acidic protein four-disulfide-core proteins in respiratory health and disease
- Substrate processing in intramembrane proteolysis by γ-secretase – the role of protein dynamics
- Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options
- Research Articles/Short Communications
- Protein Structure and Function
- Analysis of anticoagulants for blood-based quantitation of amyloid β oligomers in the sFIDA assay
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- The insect-derived antimicrobial peptide metchnikowin targets Fusarium graminearum β(1,3)glucanosyltransferase Gel1, which is required for the maintenance of cell wall integrity
- Cell Biology and Signaling
- Hypoxia-induced microRNA-146a represses Bcl-2 through Traf6/IRAK1 but not Smad4 to promote chondrocyte autophagy
- Characterization of the subcellular localization and nuclear import molecular mechanisms of herpes simplex virus 1 UL2
Articles in the same Issue
- Frontmatter
- Reviews
- The structural and functional changes of blood cells and molecular components in diabetes mellitus
- The role of whey acidic protein four-disulfide-core proteins in respiratory health and disease
- Substrate processing in intramembrane proteolysis by γ-secretase – the role of protein dynamics
- Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options
- Research Articles/Short Communications
- Protein Structure and Function
- Analysis of anticoagulants for blood-based quantitation of amyloid β oligomers in the sFIDA assay
- Stability and aggregation propensity do not fully account for the association of various germline variable domain gene segments with light chain amyloidosis
- The insect-derived antimicrobial peptide metchnikowin targets Fusarium graminearum β(1,3)glucanosyltransferase Gel1, which is required for the maintenance of cell wall integrity
- Cell Biology and Signaling
- Hypoxia-induced microRNA-146a represses Bcl-2 through Traf6/IRAK1 but not Smad4 to promote chondrocyte autophagy
- Characterization of the subcellular localization and nuclear import molecular mechanisms of herpes simplex virus 1 UL2