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pmid:30185781

Downregulation of the long noncoding RNA MBNL1-AS1 protects sevoflurane-pretreated mice against ischemia-reperfusion injury by targeting KCNMA1.

Xue-Feng Li · Zong-Qiang Wang · Long-Yun Li · Guo-Qing Zhao · Shao-Nan Yu

Experimental & molecular medicine · 2018 doi:10.1038/s12276-018-0133-y

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:30185781
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science-record
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2026-11-01T15:40:37Z
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paper object · 10 fields
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title
Downregulation of the long noncoding RNA MBNL1-AS1 protects sevoflurane-pretreated mice against ischemia-reperfusion injury by targeting KCNMA1.
doi
10.1038/s12276-018-0133-y
pmid
30185781
authors array · 5 items
[0]
Xue-Feng Li
[1]
Zong-Qiang Wang
[2]
Long-Yun Li
[3]
Guo-Qing Zhao
[4]
Shao-Nan Yu
journal
Experimental & molecular medicine
year
2018
abstract
Total knee arthroplasty (TKA) is the most common and cost-effective treatment for older adults with long-standing osteoarthritis. During TKA, muscle cells suffer from prolonged oxygen deficiency, which leads to altered cell metabolism that reduces the energy demand and maintains cell homeostasis before blood flow is restored. This study focused on the role of the lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in protecting sevoflurane-pretreated mice against ischemia-reperfusion (I/R) injury after TKA, as well as the elucidation of the potential associated mechanism. Identification of differentially expressed lncRNAs was performed using the microarray dataset GSE21164, which was extracted from the GEO database. Target genes of the lncRNA were determined using Multi-Experiment Matrix (MEM), a dual-luciferase reporter gene assay, and KEGG enrichment analyses. The results showed that MBNL1-AS1 was overexpressed in skeletal muscle cells in mice, while KCNMA1, which was enriched in the cGMP-PKG signaling pathway, was negatively regulated by MBNL1-AS1. Furthermore, I/R mice displayed serious inflammatory reactions. Down-regulation of MBNL1-AS1 increased the expression of KCNMA1, PKGII, VASP, VEGF, Bcl-2, Cyclin D1, Cyclin D3, and Cdc 42 but decreased the expression of Bax, cleaved caspase-3, and cleaved PARP. Furthermore, upon MBNL1-AS1 upregulation, the rate of cell apoptosis increased while the rate of cell proliferation decreased. Our data suggested that down-regulated lncRNA MBNL1-AS1 might promote the proliferation and inhibit the apoptosis of skeletal muscle cells by upregulating KCNMA1 expression via activation of the cGMP-PKG signaling pathway, thus protecting sevoflurane-pretreated mice against I/R injury after TKA.
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The GSE21164 microarray dataset and probe files for TKA downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) were analyzed using the Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA).
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The GSE21164 microarray dataset and probe files for TKA downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) were analyzed using the Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA).
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Expression data from total knee arthroplasty patients
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ELISA confirms LDH, TNF-α, and IL-1β are increased in mice with I/R injury after TKA
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LDH, TNF-α, and IL-1β were increased in mice with I/R injury after TKA
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ELISA confirms LDH, TNF-α, and IL-1β are increased in mice with I/R injury after TKA
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[2]
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[3]
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[1]
98.16 ± 8.92*
[2]
187.13 ± 8.27*
[3]
458.62 ± 25.52*
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[0]
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67.53 ± 5.14*#
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146.26 ± 7.42*#
[3]
314.27 ± 21.52*#
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Apoptosis rate and cell cycle distribution of skeletal muscle cells among seven groups
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MBNL1-AS1 promoted the apoptosis of skeletal muscle cells
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Apoptosis rate and cell cycle distribution of skeletal muscle cells among seven groups
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[4]
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Complete file
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During TKA, muscle cells suffer from prolonged oxygen deficiency, which leads to altered cell metabolism that reduces the energy demand and maintains cell homeostasis before blood flow is restored. This study focused on the role of the lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in protecting sevoflurane-pretreated mice against ischemia-reperfusion (I/R) injury after TKA, as well as the elucidation of the potential associated mechanism. Identification of differentially expressed lncRNAs was performed using the microarray dataset GSE21164, which was extracted from the GEO database. Target genes of the lncRNA were determined using Multi-Experiment Matrix (MEM), a dual-luciferase reporter gene assay, and KEGG enrichment analyses. The results showed that MBNL1-AS1 was overexpressed in skeletal muscle cells in mice, while KCNMA1, which was enriched in the cGMP-PKG signaling pathway, was negatively regulated by MBNL1-AS1. Furthermore, I/R mice displayed serious inflammatory reactions. Down-regulation of MBNL1-AS1 increased the expression of KCNMA1, PKGII, VASP, VEGF, Bcl-2, Cyclin D1, Cyclin D3, and Cdc 42 but decreased the expression of Bax, cleaved caspase-3, and cleaved PARP. Furthermore, upon MBNL1-AS1 upregulation, the rate of cell apoptosis increased while the rate of cell proliferation decreased. Our data suggested that down-regulated lncRNA MBNL1-AS1 might promote the proliferation and inhibit the apoptosis of skeletal muscle cells by upregulating KCNMA1 expression via activation of the cGMP-PKG signaling pathway, thus protecting sevoflurane-pretreated mice against I/R injury after TKA.", "claims": [{"id": "claim-data-access", "statement": "The GSE21164 microarray dataset and probe files for TKA downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) were analyzed using the Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30185781", "locator": "sections[4] \"Bioinformatics prediction\" paragraph 2", "quote": "The GSE21164 microarray dataset and probe files for TKA downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) were analyzed using the Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30185781"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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muscle cells", "row_count": 10, "column_count": 5}, "table": {"label": "Table 3", "caption": "Apoptosis rate and cell cycle distribution of skeletal muscle cells among seven groups", "rows": [["Group", "Apoptosis rate (%)", "G0/G1 (%)", "S (%)", "G2/M (%)"], ["Control", "6.45 ± 0.51", "71.35 ± 5.12", "18.84 ± 1.13", "9.81 ± 0.81"], ["Blank", "3.36 ± 0.32*", "53.37 ± 3.27", "35.72 ± 2.41", "10.91 ± 1.02"], ["NC", "3.47 ± 0.31*", "53.61 ± 3.62", "34.67 ± 2.71", "11.72 ± 1.11"], ["MBNL1AS1 vector", "5.21 ± 0.49*#", "62.94 ± 4.71*#", "27.14 ± 1.73*#", "9.92 ± 0.93"], ["si-MBNL1AS1#1", "1.28 ± 0.11*#", "45.42 ± 3.84*#", "43.25 ± 3.61*#", "11.33 ± 1.12"], ["si-MBNL1AS1#2", "1.22 ± 0.23*#", "43.33 ± 2.47*#", "43.33 ± 2.47*#", "43.33 ± 2.47*#"], ["si-KCNMA1#1", "5.33 ± 0.48*#", "63.16 ± 5.12", "26.33 ± 1.73", "10.51 ± 1.01"], ["si-KCNMA1#2", "4.97 + 1.1*#", "61.89 ± 3.44", "25.08 ± 1.23", "10.34 ± 1.45"], ["si-MBNL1AS1 + si-KCNMA1", "3.42 ± 1.31*", "58.72 ± 4.22", "31.15 ± 2.63", "10.13 ± 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