STAT3-regulated RhoA drives reactive astrocyte dynamics

Raffi, François

doi:10.1080/15384101.2017.1377032

Cited by 12 publications

(15 citation statements)

References 13 publications

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“…Activation of the IL-6/JAK2/STAT3 signaling pathway can lead to the upregulation and overproduction of ICAM-1 and VCAM-1 in endothelial cells 90. The phosphorylation of STAT3 can activate Ras homolog gene family member A (RhoA), which is an essential regulator, to rearrange the microfilaments and microtubules as well as inhibit the phosphorylation of endothelial nitric oxide synthase (eNOS) 93-95. eNOS phosphorylation can suppress the effect of matrix metallopeptidase 9 (MMP-9), thus downregulating the expression of ICAM-1 and VCAM-1 90.…”

Section: Physiopathological Roles Of Stat3 In Atherosclerosismentioning

confidence: 99%

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

et al. 2019

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Atherosclerosis is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases and has attracted more attention in recent years. Multiple studies have demonstrated that the signal transducer and activator of transcription 3 (STAT3) plays essential roles in the process of atherosclerosis. Moreover, aberrant STAT3 activation has been shown to contribute to the occurrence and development of atherosclerosis. Therefore, the study of STAT3 inhibitors has gradually become a focal research topic. In this review, we describe the crucial roles of STAT3 in endothelial cell dysfunction, macrophage polarization, inflammation, and immunity during atherosclerosis. STAT3 in mitochondria is mentioned as well. Then, we present a summary and classification of STAT3 inhibitors, which could offer potential treatment strategies for atherosclerosis. Furthermore, we enumerate some of the problems that have interfered with the development of mature therapies utilizing STAT3 inhibitors to treat atherosclerosis. Finally, we propose ideas that may help to solve these problems to some extent. Collectively, this review may be useful for developing future STAT3 inhibitor therapies for atherosclerosis.

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Section: Physiopathological Roles Of Stat3 In Atherosclerosismentioning

confidence: 99%

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

et al. 2019

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“…Previous studies reported that the NF-κB signaling pathway is essential for A1 polarization 17 , 36 , 37 while the STAT3 signaling pathway might promote A2 and inhibit A1 transformation 17 , 20 . Similarly, STAT3 may also be essential for glial scar formation and astrocytic neuroprotection after spinal cord injury (SCI) 13 , 32 , 38 - 40 . It is worth mentioning that whether CNTF affects the polarization of reactive astrocytes through the STAT3 signaling pathway has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

miR-21a-5p Promotes Inflammation following Traumatic Spinal Cord Injury through Upregulation of Neurotoxic Reactive Astrocyte (A1) Polarization by Inhibiting the CNTF/STAT3/Nkrf Pathway

Zhang¹,

Meng²,

Chen³

et al. 2021

Int. J. Biol. Sci.

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Reactive astrocytes are implicated in traumatic spinal cord injury (TSCI). Interestingly, naïve astrocytes can easily transform into neurotoxic reactive astrocytes (A1s) with inflammatory stimulation. Previous studies demonstrated that microRNA(miR)-21a-5p was up-regulated in spinal cord tissue after TSCI; however, it is not clear whether this affected reactive astrocyte polarization. Here, we aim to detect the effects of miR-21a-5p on the induction of A1 formation and the underlying mechanisms. Our study found that the expression of miR-21a-5p was significantly increased while that of Cntfr α was decreased, since naïve astrocytes transformed into A1s 3 days post-TSCI; the binding site between miR-21a-5p and Cntfr α was further confirmed in astrocytes. After treatment with CNTF, the levels of A1 markers decreased while that of A2 increased. The expression of A1 markers significantly decreased with the downregulation of miR-21a-5p, while Cntfr α siRNA treatment caused the opposite both in vitro and in vivo . To summarize, miR-21a-5p/Cntfr α promotes A1 induction and might enhance the inflammatory process of TSCI; furthermore, we identified, for the first time, the effect and potential mechanism by which CNTF inhibits naïve astrocytes transformation into A1s. Collectively, our findings demonstrate that targeting miR-21a-5p represents a prospective therapy for promoting the recovery of TSCI.

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“…The comparison of affected DEGs in Zeb2os KD and Zeb2 KD showed that Zeb2os KD unique genes are enriched in Wnt/β-catenin signaling (-log( p-value ) = 2.47), complement system(-log( p-value ) = 2.29) and cell cycle (-log( p-value ) = 1.97) etc. Some of the Zeb2 KD unique DEGs enriched pathways include Ephrin receptor signaling (-log( p-value ) = 2.94) and RhoA signaling (-log( p-value ) = 2.97) ( Murai and Pasquale, 2011 ; Renault-Mihara and Okano, 2017 ). Thereby, Zeb2 only mediates the effects of Zeb2os partially.…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis

Wei

You

et al. 2021

Cell Reports

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SUMMARY Spinal cord injury (SCI) is one of the most devastating neural injuries without effective therapeutic solutions. Astrocytes are the predominant component of the scar. Understanding the complex contributions of reactive astrocytes to SCI pathophysiologies is fundamentally important for developing therapeutic strategies. We have studied the molecular changes in the injury environment and the astrocyte-specific responses by astrocyte purification from injured spinal cords from acute to chronic stages. In addition to protein-coding genes, we have systematically analyzed the expression profiles of long non-coding RNAs (lncRNAs) (>200 bp), which are regulatory RNAs that play important roles in the CNS. We have identified a highly conserved lncRNA, Zeb2os , and demonstrated using functional assays that it plays an important role in reactive astrogliosis through the Zeb2os / Zeb2 / Stat3 axis. These studies provide valuable insights into the molecular basis of reactive astrogliosis and fill the knowledge gap regarding the function(s) of lncRNAs in astrogliosis and SCI.

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STAT3-regulated RhoA drives reactive astrocyte dynamics

Cited by 12 publications

References 13 publications

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

miR-21a-5p Promotes Inflammation following Traumatic Spinal Cord Injury through Upregulation of Neurotoxic Reactive Astrocyte (A1) Polarization by Inhibiting the CNTF/STAT3/Nkrf Pathway

Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis

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