Characterizing thymic stromal lymphopoietin (TSLP): a role in neurite outgrowth
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Date
2014-08-08
Authors
Verrelli, Alyssa
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Abstract
Neuropathy is a serious complication of diabetes mellitus. In particular, sensory innervation is
progressively lost as neurons degenerate distally. Many proinflammatory cytokines have been
implicated in signalling through pathways that mediate nerve regeneration. These cytokines have also
been associated with mitochondrial respiratory regulation. Mitochondrial dysfunction is increasingly
being linked to diabetic sensory neuropathy. These cytokines, therefore, may play an important role in
modulating mitochondrial function for neurite outgrowth. The aim of my work was to characterize the
function of the cytokine thymic stromal lymphopoietin (TSLP) in relation to control of sensory neuron
phenotype. I hypothesized that TSLP signals through JAK/STAT3 and AMPK pathways to modulate
mitochondrial function and induce neurite outgrowth. My objectives were: to study the effect of cytokine
TSLP on the phenotype of sensory neurons, to investigate signaling pathways activated by TSLP, and
to explore effect of TSLP on mitochondrial bioenergetics. My results demonstrated that the effect of
TSLP on normal and diabetic sensory neurons resulted in a dose-dependent induction of neurite
outgrowth. TSLP was shown to signal through the AMPK pathway. TSLP was shown to also signal
through JAK/STAT3 to induce neurite outgrowth. The mitochondrial bioenergetics of sensory neurons
as influenced by TSLP, mediated in part via JAK/STAT3 and AMPK pathways, demonstrated an
increased spare respiratory capacity meaning that TSLP enhances the ability of mitochondria to work
under high demand for energy. Therefore, the role of TSLP in enhancing mitochondrial efficiency may
be a mechanism worth targeting therapeutically, in the treatment of diabetic neuropathy and possibly
other diseases of the peripheral nervous system.
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Keywords
thymic stromal lymphopoietin, neurite outgrowth