Anti-Apoptotic Effect of MicroRNA-21 after Contusion Spinal Cord Injury in Rats
Abstract
Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). Dysregulation of microRNAs (miRNAs) has been found following SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. We analyzed the miRNA expression patterns 1 and 3 days following rat SCI using miRNA microarray. Microarray data revealed that nine miRNAs were upregulated and five miRNAs were downregulated 1 day post-injury, and that three miRNAs were upregulated and five miRNAs were downregulated 3 days post-injury, in the sites of contused when compared with sham rat spinal cords. Because miR-21 was one of the miRNAs being most significantly upregulated, we investigated its function. Knockdown of miR-21 by antagomir-21 led to attenuated recovery in hindlimb motor function, increased lesion size, and decreased tissue sparing in rats. Compared with the negative control group, treatment with antagomir-21 significantly increased apoptosis following SCI. Pro-apoptosis genes Fas ligand (FasL), phosphatase and tensin homolog (PTEN), and programmed cell death protein 4 (PDCD4) were proved to be direct targets of miR-21 in many diseases and cell types. In vivo treatment with antagomir-21 increased the expression of FasL and PTEN, but did not affect PDCD4. These results suggested that miR-21 played an important role in limiting secondary cell death following SCI, and that the protective effects of miR-21 might have been the result of its regulation on pro-apoptotic genes. Thus, miR-21 may play an important role in the pathophysiology of SCI.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
miR-21 is significantly upregulated after spinal cord injury, causes downregulation of targets FasL and PTEN, and its expression is directly related to secondary cell death following injury.
“Several groups have identified miR-21 as significantly upregulated after spinal cord injury, causing downregulation of targets FasL and PTEN, and its expression is directly related to secondary cell death following injury16–18.”
From CNS microRNA profiles: a database for cell type enriched microRNA expression across the mouse central nervous system (2020) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Most mammalian mRNAs are conserved targets of microRNAs
Friedman, R. C., Farh, K. K.-H., Burge, C. B., & Bartel, D. P. (2009) · Genome Research · doi:10.1101/gr.082701.108 · Cited by 8,462 · see citing works
The impact of microRNAs on protein output
Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., & Bartel, D. P. (2008) · Nature · doi:10.1038/nature07242 · Cited by 3,592 · see citing works
Meng, F., Henson, R., Lang, M., Wehbe, H., Maheshwari, S., Mendell, J. T., Jiang, J., Schmittgen, T. D., & Patel, T. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.02.057 · Cited by 984 · see citing works
MicroRNA expression in the adult mouse central nervous system
Bak, M., Silahtaroglu, A., Møller, M., Christensen, M., Rath, M. F., Skryabin, B., Tommerup, N., & Kauppinen, S. (2008) · RNA · doi:10.1261/rna.783108 · Cited by 463 · see citing works
Fas ligand/Fas system in the brain: regulator of immune and apoptotic responses
Choi, C., & Benveniste, E. N. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2003.08.007 · Cited by 270 · see citing works
MicroRNA‐21 protects neurons from ischemic death
Buller, B., Liu, X., Wang, X., Zhang, R. L., Zhang, L., Hozeska‐Solgot, A., Chopp, M., & Zhang, Z. G. (2010) · The FEBS Journal · doi:10.1111/j.1742-4658.2010.07818.x · Cited by 242 · cited 4× · see citing works
“FasL, a member of the TNF-a family of ligand, was one of validated targets of miR-21. miR-21 was shown to reduce the death of ischemic cortical neurons by downregulating FasL.15 Overexpression of miR-21 in transgenic mouse heart inhibited ischemia-induced upregulation of FasL expression, limited infarct size, attenuat…”
BackgroundInfluentialMicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G
Chen, Y., Liu, W., Chao, T., Zhang, Y., Yan, X., Gong, Y., Qiang, B., Yuan, J., Sun, M., & Peng, X. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.06.034 · Cited by 217 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Tang, C., Gu, Y., Wang, H., Wu, H., Wang, Y., Meng, Y., Han, Z., Gu, Y., Ma, W., Jiang, Z., et al. (2018) · Epilepsy Research · doi:10.1016/j.eplepsyres.2018.05.001 · Cited by 50 · see citing works
Pomper, N., Liu, Y., Hoye, M. L., Dougherty, J. D., & Miller, T. M. (2020) · Scientific Reports · doi:10.1038/s41598-020-61307-5 · Cited by 39 · see citing works
Ma, C., Zhang, P., & Shen, Y. (2019) · Journal of Neurorestoratology · doi:10.26599/jnr.2019.9040024 · Cited by 19 · see citing works
Maza, R. M., Barreda-Manso, M. A., Reigada, D., Silván, Á., Muñoz-Galdeano, T., Soto, A., del Águila, Á., & Nieto-Díaz, M. (2022) · Biomedicines · doi:10.3390/biomedicines10071559 · Cited by 12 · see citing works
- Authors
- Hu, J.-Z., Huang, J.-H., Zeng, L., Wang, G., Cao, M., & Lu, H.-B.
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2013-08
- Volume
- 30
- Issue
- 15
- Pages
- 1349-1360
- ISSN
- 0897-7151
- 1557-9042
- Cited by
- 128
- References
- 7
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
