TY - CHAP
T1 - A Novel Mechanism of Sigma 1 Receptor Neuroprotection
T2 - Modulation of miR-214-3p
AU - Wang, Jing
AU - Smith, Sylvia B.
N1 - Publisher Copyright:
© 2019, Springer Nature Switzerland AG.
PY - 2019
Y1 - 2019
N2 - Retinitis pigmentosa (RP) is a blinding disease for which there is no known cure. In a recent study, we reported dramatic rescue of cones in the rd10 mouse model of RP when mice were treated systemically with (+)-pentazocine ((+)-PTZ), a high-affinity ligand for sigma 1 receptor (Sig1R). The molecular mechanisms by which Sig1R provides neuroprotection are unclear. In this report, we used a miRNA PCR array to compare 84 abundantly expressed, well-characterized miRNAs in rd10/Sig1R−/− vs. rd10 and rd10 + PTZ vs. rd10 mice. We found that 13 miRNAs were significantly increased in rd10/Sig1R−/− retinas but were significantly decreased in rd10 + PTZ retinas. The miRNAs were miR-9-5p, miR-27a-3p, miR-126a-5p, miR-146a-5p, miR-10a-5p, miR-34c-5p, miR-503-5p, miR-30c-5p, miR-199-5p, miR-541-5p, miR-214-3p, miR-218-5p, and miR-335-5p. Of these, miR-214-3p is closely related to oxidative stress modulation, which is relevant to degenerative retinopathy. MiR-214-3p expression is ~fivefold higher in rd10/Sig1R−/− vs. rd10. In contrast, miR-214-3p is decreased ~twofold in rd10 + PTZ vs. rd10. Interestingly, miR-214-3p is predicted to bind to Sig1R and Nrf2, a key transcription factor for modulation of oxidative stress. To our knowledge, this is the first evidence that Sig1R may interact with miRNAs in retina. This observation is the underpinning of our hypothesis that a novel mechanism by which Sig1R mediates cone rescue is via interaction with miR-214-3p.
AB - Retinitis pigmentosa (RP) is a blinding disease for which there is no known cure. In a recent study, we reported dramatic rescue of cones in the rd10 mouse model of RP when mice were treated systemically with (+)-pentazocine ((+)-PTZ), a high-affinity ligand for sigma 1 receptor (Sig1R). The molecular mechanisms by which Sig1R provides neuroprotection are unclear. In this report, we used a miRNA PCR array to compare 84 abundantly expressed, well-characterized miRNAs in rd10/Sig1R−/− vs. rd10 and rd10 + PTZ vs. rd10 mice. We found that 13 miRNAs were significantly increased in rd10/Sig1R−/− retinas but were significantly decreased in rd10 + PTZ retinas. The miRNAs were miR-9-5p, miR-27a-3p, miR-126a-5p, miR-146a-5p, miR-10a-5p, miR-34c-5p, miR-503-5p, miR-30c-5p, miR-199-5p, miR-541-5p, miR-214-3p, miR-218-5p, and miR-335-5p. Of these, miR-214-3p is closely related to oxidative stress modulation, which is relevant to degenerative retinopathy. MiR-214-3p expression is ~fivefold higher in rd10/Sig1R−/− vs. rd10. In contrast, miR-214-3p is decreased ~twofold in rd10 + PTZ vs. rd10. Interestingly, miR-214-3p is predicted to bind to Sig1R and Nrf2, a key transcription factor for modulation of oxidative stress. To our knowledge, this is the first evidence that Sig1R may interact with miRNAs in retina. This observation is the underpinning of our hypothesis that a novel mechanism by which Sig1R mediates cone rescue is via interaction with miR-214-3p.
KW - Cone photoreceptor cells
KW - MicroRNA
KW - Neuroprotection
KW - Nrf2
KW - Oxidative stress
KW - Retinal degeneration
KW - Retinitis pigmentosa
KW - Sigma 1 receptor
KW - miR-214-3p
UR - http://www.scopus.com/inward/record.url?scp=85077332710&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077332710&partnerID=8YFLogxK
U2 - 10.1007/978-3-030-27378-1_76
DO - 10.1007/978-3-030-27378-1_76
M3 - Chapter
C2 - 31884655
AN - SCOPUS:85077332710
T3 - Advances in Experimental Medicine and Biology
SP - 463
EP - 467
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -