Reduction of follistatin-like 1 in primary afferent neurons contributes to neuropathic pain hypersensitivity

Li, Kaicheng; Feng, Wenran; Zhong, Yan-Qing; Lu, Yao; Wang, Qiong; Zhang, Fang-Xiong; Xiao, Huasheng; Liu, Bao

doi:10.1038/cr.2011.43

Cited by 21 publications

(19 citation statements)

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“…The mechanisms for maintaining the inflammation-induced mechanical allodynia have been largely unclear, though some factors such as activin C released from small DRG neurons can partially alleviate mechanical allodynia [40]. FSTL1 did not reduce the inflammation-induced nociceptive responses (data not shown), although it reduced the mechanical allodynia induced by nerve injury [8]. Thus, FXYD2 regulation may contribute to a fundamental mechanism underlying the persistence of mechanical pain following inflammation.…”

Section: Fxyd2 Is Required For Maintaining Inflammation-induced Mechamentioning

confidence: 92%

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FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation

Feng

Cai

et al. 2015

Cell Res

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Na+ ,K + -ATPase (NKA) is required to generate the resting membrane potential in neurons. Nociceptive afferent neurons express not only the α and β subunits of NKA but also the γ subunit FXYD2. However, the neural function of FXYD2 is unknown. The present study shows that FXYD2 in nociceptive neurons is necessary for maintaining the mechanical allodynia induced by peripheral inflammation. FXYD2 interacted with α1NKA and negatively regulated the NKA activity, depolarizing the membrane potential of nociceptive neurons. Mechanical allodynia initiated in FXYD2-deficient mice was abolished 4 days after inflammation, whereas it persisted for at least 3 weeks in wild-type mice. Importantly, the FXYD2/α1NKA interaction gradually increased after inflammation and peaked on day 4 post inflammation, resulting in reduction of NKA activity, depolarization of neuron membrane and facilitation of excitatory afferent neurotransmission. Thus, the increased FXYD2 activity may be a fundamental mechanism underlying the persistent hypersensitivity to pain induced by inflammation. Keywords: FXYD2; Na

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Section: Fxyd2 Is Required For Maintaining Inflammation-induced Mechamentioning

confidence: 92%

“…NKA can be inhibited by plant cardiac glycosides such as ouabain and digoxin [5] and digitalis-like steroid hormones released from the adrenal gland [6]. Recent studies show that the α1 subunit-containing NKA (α1NKA) can be activated directly by an endogenous protein, follistatin-like 1 (FSTL1) [7,8].…”

Section: Introductionmentioning

confidence: 99%

FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation

Feng

Cai

et al. 2015

Cell Res

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“…They represent the first report describing FSTL-1 and the response to infection, in our study the spirochete B. burgdorferi . This infection likely serves as an excellent model to explore the role of FSTL-1 in response to pathogens, as FSTL-1 has been shown to be highly expressed in neurologic [19,20], cardiac [21–23] and other connective tissues [24,25], mostly of the mesenchymal lineage; all tissues targeted during B. burgdorferi infection. Further, FSTL-1 expression and function has been correlated with important non-infectious processes including sensory neuron signaling [20] and cardiomyocyte function [26], suggesting that FSTL-1 functions in normal development and physiology as well as mediating pathology.…”

Section: Discussionmentioning

confidence: 99%

Follistatin-like protein 1 is a critical mediator of experimental Lyme arthritis and the humoral response to Borrelia burgdorferi infection

Campfield

Nolder

Marinov

et al. 2014

Microbial Pathogenesis

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Follistatin-like protein 1 (FSTL-1) has recently been described as a critical mediator of CIA and a marker of disease activity. Lyme arthritis, caused by Borrelia burgdorferi, shares similarities with autoimmune arthritis and the experimental murine model collagen-induced arthritis (CIA). Because FSTL-1 is important in CIA and autoimmune arthritides, and Lyme arthritis shares similarities with CIA, we hypothesized that FSTL-1 may be an important mediator of Lyme arthritis. We demonstrate for the first time that FSTL-1 is induced by B. burgdorferi infection and is required for the development of Lyme arthritis in a murine model, utilizing a gene insertion to generate FSTL-1 hypomorphic mice. Using qPCR and qRT-PCR, we found that despite similar early infectious burden, FSTL-1 hypomorphic mice have improved spirochetal clearance in the face of attenuated arthritis and inflammatory cytokine production. Further, FSTL-1 mediates pathogen-specific antibody production and antigen recognition when assessed by ELISA and one- and two-dimensional immunoblotting. This study is the first to describe a role for FSTL-1 in the development of Lyme arthritis and anti-Borrelia response, and the first to demonstrate a role for FSTL-1 in response to infection, highlighting the potential for FSTL-1 as a target in the treatment of B. burgdorferi infection.

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“…FGF13 is expressed in 60% of DRG neurons under normal circumstances [23]. It has been shown that the gene expression profiles of DRG and the dorsal spinal cord are modified by peripheral nerve injury, leading to gene-regulation of many molecules, such as neurotransmitter receptors, ion channels and the Na + ,K + -ATPase activator [25][26][27][28][29][30]. Indeed, after sciatic nerve transection, the expression of FGF2 and FGF7 increased in the DRG, whereas FGF13 expression decreased [23,24].…”

Section: Expression Of Intracellular Fgfs In the Nervous Systemmentioning

confidence: 99%

Roles of intracellular fibroblast growth factors in neural development and functions

Liu

et al. 2012

Sci. China Life Sci.

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Fibroblast growth factors (FGFs) can be classified as secretory (FGF1-10 and FGF15-23) or intracellular non-secretory forms (FGF11-14). Secretory forms of FGF and their receptors are best known for their regulatory roles in cell growth, differentiation and morphogenesis in the early stages of neural development. However, the functions of intracellular FGFs remain to be explored. FGF12 and FGF14 are found to interact with voltage-gated sodium channels, and regulate the channel activity in neurons. FGF13 is expressed in primary sensory neurons, and is colocalized with sodium channels at the nodes of Ranvier along the myelinated afferent fibers. FGF13 is also expressed in cerebral cortical neurons during the late developmental stage. A recent study showed that FGF13 is a microtubule-stabilizing protein required for regulating the neuronal development in the cerebral cortex. Thus, non-secretory forms of FGF appear to have important roles in the brain, and it would be interesting to further investigate the functions of intracellular FGFs in the nervous system and in neural diseases. fibroblast growth factors, nervous system, development, microtubule, ion channel, X-linked mental retardation Citation:Zhang X, Bao L, Yang L, et al. Roles of intracellular fibroblast growth factors in neural development and functions.

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Reduction of follistatin-like 1 in primary afferent neurons contributes to neuropathic pain hypersensitivity

Cited by 21 publications

References 9 publications

FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation

FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation

Follistatin-like protein 1 is a critical mediator of experimental Lyme arthritis and the humoral response to Borrelia burgdorferi infection

Roles of intracellular fibroblast growth factors in neural development and functions

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