Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

Modi, Khushbu K.; Sendtner, Michael; Pahan, Kalipada

doi:10.1074/jbc.m112.447268

Cited by 46 publications

(55 citation statements)

References 38 publications

(68 reference statements)

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“…3a), though a much higher concentration of ASA (i.e., 5 μM) could significantly increase CNTF mRNA levels in astrocyte cultures (Fig. 3b), that agreed with the previous report [14]. The ELISA analysis of the culture media further confirmed that ASA did not significantly upregulate CNTF secretion in OPCs (Fig.…”

Section: Aspirin Promotes In Vitro Oligodendroglial Differentiation Bsupporting

confidence: 92%

“…In addition to its effects on anti-inflammation and/or neuroprotection [38,13], ASA also exert indirect effect on remyelination through upregulation of astrocytic CNTF [14] and direct effect on oligodendroglial differentiation as demonstrated in this study. These findings suggest that ASA may be a novel candidate for the treatment of demyelinating diseases, such as MS.…”

Section: Discussionmentioning

confidence: 69%

“…For instance, ASA can reduce oxygen radicals and inhibit the aggregation of amyloid-beta or increase the expression of neuregulin1 for neural survival [12,13,32,33]. Most recently, it was found that ASA can promote astrocytic secretion of CNTF [14]. Notably, besides its neurotrophic effect, CNTF also exerts positive effects on OL differentiation through activation of the JNK signaling pathway [15].…”

Section: Discussionmentioning

confidence: 97%

“…Accordingly, ASA has also been utilized for the treatment of neurodegenerative diseases or neurological disorders such as Alzheimer's disease and schizophrenia [12,13]. Recently, ASA was reported to upregulate the secretion of astrocytic CNTF, which has the capacity to enhance the survival of oligodendroglial lineage cells and to promote expression of myelin-associated proteins, e.g., proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) [14,15]. A most recent study using white matter lesion (WML) model demonstrated that low concentrations of aspirin can promote OPC proliferation while high concentrations of aspirin usage induce OPC differentiation [16], suggesting potential effects of ASA on oligodendroglial lineage.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway

Huang

Dong

et al. 2015

Mol Neurobiol

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Aspirin, one of the most commonly used anti-inflammatory drugs, has been recently reported to display multiple effects in the central nervous system (CNS), including neuroprotection and upregulation of ciliary neurotrophic factor (CNTF) expression in astrocytes. Although it was most recently reported that aspirin could promote the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) after white matter lesion, the underlying mechanisms remain unclear. To dissect the effects of aspirin on oligodendroglial development and explore possible mechanisms, we here demonstrated the following: (i) in vitro treatment of aspirin on OPC cultures significantly increased the number of differentiated oligodendrocytes (OLs) but had no effect on the number of proliferative OPCs, indicating that aspirin can promote OPC differentiation but not proliferation; (ii) in vivo treatment of aspirin on neonatal (P3) rats for 4 days led to a nearly twofold increase in the expression of myelin basic protein (MBP), devoid of change in OPC proliferaion, in the corpus callosum (CC); (iii) finally, aspirin treatment increased the phosphorylation level of β-catenin and counteracted Wnt signaling pathway synergist QS11-induced suppression on OPC differentiation. Together, our data show that aspirin can directly target oligodendroglial lineage cells and promote their differentiation through inhibition of Wnt/β-catenin signaling pathway. These findings suggest that aspirin may be a novel candidate for the treatment of demyelinating diseases.

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Section: Aspirin Promotes In Vitro Oligodendroglial Differentiation Bsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway

Huang

Dong

et al. 2015

Mol Neurobiol

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“…Given the counteractive effect of the cAMP/ PKA pathway on the RhoA/ROCK pathway [17], an increased cAMP/PKA level could inhibit RhoA/ROCK signaling and would thus be another mechanism underlying the enhanced neuroregeneration by MAT treatment. Furthermore, the cAMP/PKA signaling pathway is an important mechanism for the induction of neurotrophic factors that promote neural development and regeneration [48]. Importantly, upon MAT treatment, significantly enhanced cAMP/PKA expression was obtained in vitro in primary astrocytes, indicating an immunomodulation-independent mechanism of MAT in the induction of the cAMP/PKA pathway.…”

Section: Discussionmentioning

confidence: 98%

Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis

Kan

Zhang

et al. 2016

Mol Neurobiol

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Myelin-associated inhibitors, such as NogoA, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), play a pivotal role in the lack of neuroregeneration in multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). Matrine (MAT), a monomer that is used in traditional Chinese medicine as an anti-inflammatory agent, has shown beneficial effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, the underlying mechanisms of MAT-induced EAE amelioration are not fully understood. In the present study, we show that MAT treatment suppressed ongoing EAE, and this effect correlated with an increased expression of growth-associated protein 43, an established marker for axonal regeneration. MAT treatment significantly reduced the levels of NogoA, its receptor complex NgR/p75NTR/LINGO-1, and their downstream RhoA/ROCK signaling pathway in the CNS. In contrast, intracellular cyclic AMP (cAMP) levels and its protein kinase (protein kinase A (PKA)), which can promote axonal regrowth by inactivating the RhoA, were upregulated. Importantly, adding MAT in primary astrocytes in vitro largely induced cAMP/PKA expression, and blockade of cAMP significantly diminished MAT-induced expression of PKA and production of BDNF, a potent neurotrophic factor for neuroregeneration. Taken together, our findings demonstrate that the beneficial effects of MAT on EAE can be attributed not only to its capacity for immunomodulation, but also to its directly promoting regeneration of the injured CNS.

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All‐trans retinoic acid upregulates the expression of ciliary neurotrophic factor in retinal pigment epithelial cells

Zhou

Wang

Zhou

et al. 2017

Cell Biochemistry & Function

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Retinopathy of prematurity, a leading cause of visual impairment in low birth-weight infants, remains a crucial therapeutic challenge. Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor that promotes rod and cone photoreceptor survival and cone outer segment regeneration in the degenerating retina. Ciliary neurotrophic factor expression is regulated by many factors such as all-trans retinoic acid (ATRA). In this study, we found that ATRA increased CNTF expression in mouse retinal pigment epithelial (RPE) cells in a dose- and time-dependent manner, and PKA signaling pathway is necessary for ATRA-induced CNTF upregulation. Furthermore, we showed that ATRA promoted CNTF expression through CREB binding to its promoter region. In addition, CNTF levels were decreased in serum of retinopathy of prematurity children and in retinal tissue of oxygen-induced retinopathy mice. In mouse RPE cells cultured with high oxygen, CNTF expression and secretion were decreased, but could be recovered after treatment with ATRA. In conclusion, our data suggest that ATRA administration upregulates CNTF expression in RPE cells.

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Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

Cited by 46 publications

References 38 publications

Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway

Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway

Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis

All‐trans retinoic acid upregulates the expression of ciliary neurotrophic factor in retinal pigment epithelial cells

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