MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome
Abstract
:1. Introduction
2. Mechanisms Leading to Tissue Damage in ALI/ARDS
2.1. PRRs and Related Molecules in ALI/ARDS
2.1.1. TLRs
2.1.2. NLRs
2.2. Inflammation-Related Pathways of ALI/ARDS
2.2.1. TLRs Mediate NF-κB Signaling Pathway
2.2.2. JAK2/STAT3 Signal Pathway
2.2.3. The Role and Signaling Pathway of the NLRP3 Inflammasome in ALI/ARDS
2.2.4. PI3K/AKT Signaling Pathway
2.2.5. p38 MAPΚ Signaling Pathway
3. The Role of MicroRNAs in LPS-Induced ALI/ARDS
3.1. Biogenesis and Biological Function of MiRNAs
3.2. Adverse Inflammation-Related MiRNAs
3.3. Protective Inflammation-Associated MiRNAs
3.3.1. Targeting ALI/ARDS through NF-κB Signaling Pathway
3.3.2. Targeting ALI/ARDS through JAK2/STAT3 Signaling Pathway
3.3.3. Targeting ALI/ARDS by Regulating NLRP3 Signaling Pathway
3.3.4. Targeting ALI/ARDS through PI3Κ/AKT Signaling Pathway
Type | MicroRNA | Damage Factors | Target | Expression | Function | Signaling Pathway | Reference |
---|---|---|---|---|---|---|---|
Adverse | miR-34a | LPS | FOXO3 | upregulation | Proinflammatory | NF-κB signaling pathway | [84] |
miR-34a | hyperoxia | Ang1 | upregulation | Proinflammatory | NF-κB signaling pathway | [85] | |
miR-326 | LPS | BCL2A1 | upregulation | Proinflammatory | NF-κB signaling pathway | [87] | |
miR-300 | LPS | IκBα | upregulation | Proinflammatory | NF-κB signaling pathway | [88] | |
miR-132 | SEB | FOXO3 | upregulation | Proinflammatory | NF-κB signaling pathway | [90] | |
miR-155 | LPS | SOCS1 | upregulation | Proinflammatory | NF-κB signaling pathway | [93] | |
miR-155 | LPS | C/EBPb and IL-13R | upregulation | Proinflammatory | regulates M1/M2 polarization | [94] | |
miR-887-3p | LPS | upregulation | Proinflammatory | [96] | |||
miR-34a-5p | LPS and hyperoxia | SIRT1 | upregulation | Proinflammatory | [121] | ||
miR-1246 | LPS | ACE2 | upregulation | Proinflammatory | [122] | ||
miR-92a | LPS | ITGA5 | upregulation | Proinflammatory | PI3Κ/AKT signaling pathway | [119] | |
miR-34b-5p | LPS | PGRN | upregulation | Proinflammatory | [123] | ||
miR-199a | LPS | SIRT1 | upregulation | Proinflammatory | [124] | ||
miR-181b | LPS | P65 | upregulation | Proinflammatory | NF-κB signaling pathway | [108,109] | |
miR-127 | LPS | BCL6 | upregulation | Proinflammatory | P38 MAPK signaling pathway | [94] | |
Protective | miR-27a | LPS | TLR4 | downregulation | anti-inflammatory | NF-κB signaling pathway | [99,100] |
miR-16 | LPS | TLR4 | downregulation | anti-inflammatory | NF-κB signaling pathway | [102] | |
miR-182 | LPS | downregulation | anti-inflammatory | NF-κB signaling pathway | [103] | ||
miR-145-5p | LPS | TLR4 | downregulation | anti-inflammatory | NF-κB signaling pathway | [125] | |
miR-140 | LPS | TLR4 | downregulation | anti-inflammatory | NF-κB signaling pathway | [126] | |
miR-140-5p | LPS | TLR4 | downregulation | anti-inflammatory | NF-κB signaling pathway | [127] | |
miR-146a | LPS | IRAK1 TRAF6 | downregulation | anti-inflammatory | NF-κB signaling pathway | [104] | |
miR-146b | LPS | IRAK1 | downregulation | anti-inflammatory | NF-κB signaling pathway | [105] | |
miR-181b | LPS | importin-α3 | downregulation | anti-inflammatory | NF-κB signaling pathway | [107] | |
miR-124-3p | LPS | p65 | downregulation | anti-inflammatory | NF-κB signaling pathway | [106] | |
miR-21 | LPS | JAK2 | downregulation | anti-inflammatory | JAK2/STAT3 and NF-κB signaling pathways | [110] | |
miR-216a | LPS | JAK2 | downregulation | anti-inflammatory | JAK2/STAT3 signal pathway | [111] | |
miR-30b-5p | LPS | SOCS3 | downregulation | anti-inflammatory | JAK2/STAT3 signal pathway | [112] | |
miR-127 | LPS | CD64 | downregulation | anti-inflammatory | STAT3 signaling pathway | [114] | |
miR-495 | LPS | NLRP3 | downregulation | anti-inflammatory | NLRP3 signaling pathway | [73] | |
miR-802 | LPS | Peli2 | downregulation | anti-inflammatory | NLRP3 signaling pathway | [117] | |
miR-223 | LPS | NLRP3 | downregulation | anti-inflammatory | NLRP3 signaling pathway | [73,118] | |
miR-21a-3p | LPS | downregulation | anti-inflammatory | PI3K (p110α)/Akt/mTOR pathway | [120] |
3.4. Acute Lung Injury/Acute Respiratory Distress Syndrome and Exosomal MicroRNAs
4. The Potential Role of MiRNAs in Clinical Treatment of ALI/ARDS
Name (Company) | Therapeutic Agent | Target Diseases | Trial Details | Clinical Trials.Gov Identifier | Reference |
---|---|---|---|---|---|
Mirvirasen (Santaris Pharma A/S and Hoffmann-La Roche) | Anti-miR-122 | Hepatitis C (chronic infections included) | Phase III, completed | NCT01728324 | [78,135] |
Phase III, completed | NCT01366638 | ||||
Phase IV, completed | NCT01222611 | ||||
Phase II, completed | NCT00996476 | ||||
Phase III, completed | NCT01725529 | ||||
Phase III, completed | NCT01290731 | ||||
Phase III, completed | NCT01292239 | ||||
Phase III, completed | NCT01288209 | ||||
metastatic soft tissue sarcoma | Phase II, completed | NCT00413192 | [139] | ||
Cobomarsen or MRG-106 (miRagen Therapeutics) | Anti-miR-155 | cutaneous T-lymphoma, Alibell’s disease, chronic lymphocytic leukemia and adult T-cell leukemia and lymphoma | Phase I, completed | NCT02580552 | [146] |
CDR132L | miR-132 inhibitor | heart disease | Phase I, completed | NCT04045405 | [149] |
MRX34 (Mirna Therapeutics) | miR-34 mimic | multiple solid tumours | Multicentre phase I, terminated | NCT01829971 | [141,142,143,144,145] |
MesomiR-1 (EnGeneIC) | miR-16 mimic | mesothelioma, non-small cell lung cancer | Phase I, completed | NCT02369198 | [135] |
Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) | Recruiting | NCT03766204 |
5. Summary and Future Prospects
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Lu, Q.; Yu, S.; Meng, X.; Shi, M.; Huang, S.; Li, J.; Zhang, J.; Liang, Y.; Ji, M.; Zhao, Y.; et al. MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome. Int. J. Mol. Sci. 2022, 23, 5545. https://doi.org/10.3390/ijms23105545
Lu Q, Yu S, Meng X, Shi M, Huang S, Li J, Zhang J, Liang Y, Ji M, Zhao Y, et al. MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome. International Journal of Molecular Sciences. 2022; 23(10):5545. https://doi.org/10.3390/ijms23105545
Chicago/Turabian StyleLu, Qianying, Sifan Yu, Xiangyan Meng, Mingyu Shi, Siyu Huang, Junfeng Li, Jianfeng Zhang, Yangfan Liang, Mengjun Ji, Yanmei Zhao, and et al. 2022. "MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome" International Journal of Molecular Sciences 23, no. 10: 5545. https://doi.org/10.3390/ijms23105545