scholarly journals Failure to Upregulate the RNA Binding Protein ZBP After Injury Leads to Impaired Regeneration in a Rodent Model of Diabetic Peripheral Neuropathy

2021 ◽  
Vol 14 ◽  
Author(s):  
James I. Jones ◽  
Christopher J. Costa ◽  
Caitlin Cooney ◽  
David C. Goldberg ◽  
Matthew Ponticiello ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Rodent Model ◽  
Dorsal Root Ganglion Neurons ◽  
Nerve Degeneration ◽  
Type I ◽  
Ganglion Neurons

Most diabetes patients eventually suffer from peripheral nerve degeneration. Unfortunately, there is no treatment for the condition and its mechanisms are not well understood. There is, however, an emerging consensus that the inability of peripheral nerves to regenerate normally after injury contributes to the pathophysiology. We have previously shown that regeneration of peripheral axons requires local axonal translation of a pool of axonal mRNAs and that the levels and members of this axonal mRNA pool are altered in response to injury. Here, we show that following sciatic nerve injury in a streptozotocin rodent model of type I diabetes, this mobilization of RNAs into the injured axons is attenuated and correlates with decreased axonal regeneration. This failure of axonal RNA localization results from decreased levels of the RNA binding protein ZBP1. Over-expression of ZBP1 rescues the in vitro growth defect in injured dorsal root ganglion neurons from diabetic rodents. These results provide evidence that decreased neuronal responsiveness to injury in diabetes is due to a decreased ability to alter the pool of axonal mRNAs available for local translation, and may open new therapeutic opportunities for diabetic peripheral neuropathy.

scholarly journals The RNA-binding protein HuR/ELAVL1 regulates IFN-β mRNA abundance and the type I IFN response

2015 ◽  
Vol 45 (5) ◽  
pp. 1500-1511 ◽  
Author(s):  
Barbara Herdy ◽  
Thomas Karonitsch ◽  
Gregory I. Vladimer ◽  
Chris S.H. Tan ◽  
Alexey Stukalov ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mrna Abundance ◽  
Type I ◽  
Type I Ifn

scholarly journals The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Rebecca Mahony ◽  
Lindsay Broadbent ◽  
Jacen S. Maier-Moore ◽  
Ultan F. Power ◽  
Caroline A. Jefferies
Keyword(s):  
Viral Infection ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Type I ◽  
Type Iii ◽  
Type Iii Ifn

scholarly journals The RNA-Binding Protein KSRP Modulates Cytokine Expression of CD4+ T Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Rudolf Käfer ◽  
Lisa Schmidtke ◽  
Katharina Schrick ◽  
Evelyn Montermann ◽  
Matthias Bros ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cytokine Expression ◽  
Negative Regulator ◽  
Control Group ◽  
Type I

The KH-type splicing regulatory protein (KSRP) is a RNA-binding protein, which regulates the stability of many mRNAs encoding immune-relevant proteins. As KSRP regulates innate immune responses, for instance by the modulation of type I interferon mRNA stability, we were interested whether knockdown of the protein (KSRP-/-) interferes with T cell activation and polarization. Polyclonally stimulated KSRP-/- CD4+ T cells proliferated at a higher extent and higher frequency and expressed the activation marker CD25 more than wild-type T cells. In supernatants of stimulated KSRP-/- CD4+ T cells, levels of IL-5, IL-9, IL-10, and IL-13 were observed to be increased compared to those of the control group. KSRP-/- CD8+ T cells showed no altered proliferative capacity upon polyclonal stimulation, but supernatants contained lower levels of interferon-γ. Similar changes in the cytokine expression patterns were also detected in T cells derived from KSRP-/- mice undergoing arthritis induction indicative of a pathophysiological role of KSRP-dependent T cell polarization. We demonstrated the direct binding of KSRP to the 3′ untranslated region of IL-13, IL-10, and IFN-γ mRNA in in vitro experiments. Moreover, since IL-4 mRNA decay was reduced in KSRP-/- CD4+ T cells, we identify KSRP as a negative regulator of IL-4 expression. These data indicate that overexpression of IL-4, which constitutes the primary inducer of Th2 polarization, may cause the Th2 bias of polyclonally stimulated KSRP-/- CD4+ T cells. This is the first report demonstrating that KSRP is involved in the regulation of T cell responses. We present strong evidence that T cells derived from KSRP-/- mice favor Th2-driven immune responses.

Longitudinal RNA sequencing of skin and DRG neurons in mice with paclitaxel-induced peripheral neuropathy

2021 ◽  
Author(s):  
Anthony M. Cirrincione ◽  
Cassandra A. Reimonn ◽  
Benjamin J Harrison ◽  
Sandra Rieger
Keyword(s):  
Peripheral Neuropathy ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Recovery Phase ◽  
Dorsal Root Ganglion Neurons ◽  
Therapeutic Interventions ◽  
Nerve Degeneration ◽  
Regulatory Changes ◽  
Underlying Mechanisms ◽  
Ganglion Neurons

Abstract Paclitaxel-induced peripheral neuropathy is a condition of nerve degeneration induced by chemotherapy, which afflicts up to 70% of treated patients. Therapeutic interventions are unavailable due to an incomplete understanding of the underlying mechanisms. We previously discovered that major physiological changes in the skin underlie paclitaxel-induced peripheral neuropathy in zebrafish and rodents. The precise molecular mechanisms are only incompletely understood. For instance, paclitaxel induces the upregulation of MMP-13, which when inhibited prevents axon degeneration. To better understand other gene regulatory changes induced by paclitaxel, we induced peripheral neuropathy in mice following intraperitoneal injection either with vehicle or paclitaxel every other day four times total. Skin and dorsal root ganglion neurons were collected based on distinct behavioural responses categorized as “pain onset” (d4), “maximal pain” (d7), “beginning of pain resolution” (d11) and “recovery phase” (d23) for comparative longitudinal RNA sequencing. The generated datasets validate previous discoveries and reveal additional gene expression changes that warrant further validation with the goal to aid in development of drugs that prevent or reverse paclitaxel-induced peripheral neuropathy.

235: The RNA-Binding Protein IMP3: A Novel Molecular Marker Predicts Progression of Superficial (TA and T1) Urothelial Carcinomas of Bladder

2007 ◽  
Vol 177 (4S) ◽  
pp. 78-79
Author(s):  
Lioudmila Sitnikova ◽  
Gary Mendese ◽  
Qin Lui ◽  
Bruce A. Woda ◽  
Di Lu ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Urothelial Carcinomas
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