Downregulation of MicroRNA-145-5p in Activated Microglial Exosomes Promotes Astrocyte Proliferation by Removal of Smad3 Inhibition

Ye, Yong; Hao, Jie; Zhou, Hong; Wu, Tong; Ge, Xingyu; Qian, Boyu; Chen, Xiaoqing; Zhang, Feng

doi:10.1007/s11064-021-03446-3

Cited by 9 publications

(5 citation statements)

References 41 publications

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“…For instance, hsa-miR-145-5p expression is significantly increased in neonates with poor neurodevelopmental outcomes after asphyxia [77]. What's more, it was found to be a negative regulator of astrocyte proliferation, and its downregulation promoted smad3 activity, which in turn promoted astrocyte proliferation [89]. In vitro experiments showed that the potent inflammatory agent lipopolysaccharide (LPS) down-regulated miR-145 expression in astrocytes isolated from neonatal spinal cord tissues, and it was also suggested that miR-145 potentially targets GFAP and c-myc to inhibit inflammation-induced astrocyte proliferation [90].…”

Section: Mirnasmentioning

confidence: 98%

Role and Therapeutic Potential of Non-coding RNAs in Astrocytes during Neonatal Brain Injury

Ye,

Yuan

2023

Preprint

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Perinatal brain injury is a major public health problem burdened with high morbidity, mortality and severe neurological sequelae. Despite advances in neonatal life-saving technologies, neonatal encephalopathy lacks specific and effective treatment. Therefore, mechanisms of central nervous system changes associated with perinatal brain injury have been a hot topic of neonatology research. In recent years, researchers have shifted more focus from neurons themselves to perineuronal cells and intercellular interactions. As a member of the nervous system network, astrocytes are one of the dominant glial cells that regulate ion homeostasis, blood flow, and antioxidant function in the brain. Their changes in molecular mechanisms (e.g., alterations in RNA regulatory networks) during brain injury storms deserve further attention. Non-coding RNAs participate in and promote reactive pathophysiologic changes in astrocytes. The review summarizes and discusses the role of non-coding RNAs in astrocytes in recent years in studies of neonatal brain injury. It focuses on the most studied disease-related ncRNAs: miRNAs, lncRNAs and circRNAs, and hopes to provide possible directions for pathophysiological studies and therapeutic approaches of neonatal brain injury.

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Section: Mirnasmentioning

confidence: 98%

Role and Therapeutic Potential of Non-coding RNAs in Astrocytes during Neonatal Brain Injury

Ye,

Yuan

2023

Preprint

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“…These findings indicate that miR-145 could prevent spinal cord tissue injury by promoting astrocyte proliferation and glial scar formation ( Wang et al, 2015 ). Similarly, miR-145-5p is a negative regulator of astrocyte proliferation, and its downregulation promotes SMAD3 activity, thereby promoting astrocyte proliferation and glial scar formation ( Ye et al, 2022 ). LncRNAH19 as ceRNA could attenuate the inhibitory effect of miR-1-3p on C-C motif chemokine ligand 2 (CCL2) expression in SCI.…”

Section: Micrornas Regulate the Activities And Functions Of Reactive ...mentioning

confidence: 99%

“…The downregulation of miR-124 expression promotes reactive astrocyte proliferation and glial scar formation in ischemic stroke ( Li Z. et al, 2021 ). miR-124, miR-145-5p, miR-1-3p, and miR-17-5p could regulate glial scar formation in SCI ( Hong et al, 2014 ; Li P. et al, 2020 ; Li Z. et al, 2021 ; Ye et al, 2022 ). miR-124, miR-145-5p, miR-1-3p, and miR-17-5p could be used as indicators of the extent of glial scar formation.…”

Section: Clinical Applications Of Microrna-targeted Regulation Of Rea...mentioning

confidence: 99%

MicroRNA-mediated regulation of reactive astrocytes in central nervous system diseases

Fan

Huang

Shao

et al. 2023

Front. Mol. Neurosci.

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Astrocytes (AST) are abundant glial cells in the human brain, accounting for approximately 20–50% percent of mammalian central nervous system (CNS) cells. They display essential functions necessary to sustain the physiological processes of the CNS, including maintaining neuronal structure, forming the blood–brain barrier, coordinating neuronal metabolism, maintaining the extracellular environment, regulating cerebral blood flow, stabilizing intercellular communication, participating in neurotransmitter synthesis, and defending against oxidative stress et al. During the pathological development of brain tumors, stroke, spinal cord injury (SCI), neurodegenerative diseases, and other neurological disorders, astrocytes undergo a series of highly heterogeneous changes, which are called reactive astrocytes, and mediate the corresponding pathophysiological process. However, the pathophysiological mechanisms of reactive astrocytes and their therapeutic relevance remain unclear. The microRNAs (miRNAs) are essential for cell differentiation, proliferation, and survival, which play a crucial role in the pathophysiological development of CNS diseases. In this review, we summarize the regulatory mechanism of miRNAs on reactive astrocytes in CNS diseases, which might provide a theoretical basis for the diagnosis and treatment of CNS diseases.

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“…Moreover, miR-124-3p has a regulatory effect on macrophages in addition to microglia and can also ameliorate neurological damage caused by SCI by inhibiting Ern1 expression and enhancing M2 polarization [ 31 ]. In addition, miR-145-3p plays a negative regulatory role in the regulation of astrocyte proliferation downregulating smad3 protein activity [ 58 ]. It was also shown that bone marrow-derived, exosomal microRNA-125a can promote M2 macrophage polarization in SCI by downregulating IRF5 [ 31 ].…”

Section: The Role Of Exosome-loaded Mirnas In the Pathophysiology Of Scimentioning

confidence: 99%

The Importance of Using Exosome-Loaded miRNA for the Treatment of Spinal Cord Injury

Shen

Cai

2022

Mol Neurobiol

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Spinal cord injury (SCI) is a major traumatic disease of the central nervous system characterized by high rates of disability and mortality. Many studies have shown that SCI can be divided into the two stages of primary and secondary injury. Primary injury leads to pathophysiological changes, while consequential injury is even more fatal, including a series of harmful reactions that expand the scope and degree of SCI. Because the pathological process of SCI is highly complex, there is still no clear and effective clinical treatment strategy. Exosomes, membrane-bound extracellular vesicles (EVs) with a diameter of 30–200 nm, have emerged as an ideal vector to deliver therapeutic molecules. At the same time, increasing numbers of studies have shown that miRNAs play a momentous role in the process of SCI. In recent studies, researchers have adopted exosomes as carriers of miRNAs with potential therapeutic effects in SCI. In this review, we summarize relevant articles describing exosomes as miRNA carriers for SCI, after which we discuss further implications and perspectives of this novel treatment modality.

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Downregulation of MicroRNA-145-5p in Activated Microglial Exosomes Promotes Astrocyte Proliferation by Removal of Smad3 Inhibition

Cited by 9 publications

References 41 publications

Role and Therapeutic Potential of Non-coding RNAs in Astrocytes during Neonatal Brain Injury

Role and Therapeutic Potential of Non-coding RNAs in Astrocytes during Neonatal Brain Injury

MicroRNA-mediated regulation of reactive astrocytes in central nervous system diseases

The Importance of Using Exosome-Loaded miRNA for the Treatment of Spinal Cord Injury

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