PDX1, a transcription factor essential for organ differentiation, regulates SERCA-dependent Ca 2+ homeostasis in sensory neurons.

Autor: Saloman JL; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Neurobiology, Center for Neuroscience and Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: jls354@pitt.edu., Epouhe AY; Department of Neurobiology, Center for Neuroscience and Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Ruff CF; Department of Neurobiology, Center for Neuroscience and Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Albers KM; Department of Neurobiology, Center for Neuroscience and Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jazyk: angličtina
Zdroj: Cell calcium [Cell Calcium] 2024 Jun; Vol. 120, pp. 102884. Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1016/j.ceca.2024.102884
Abstrakt: Pancreatic and duodenal homeobox 1 (PDX1) is a transcription factor required for the development and differentiation of the pancreas. Previous studies indicated that PDX1 expression was restricted to the gastrointestinal tract. Using a cre-dependent reporter, we observed PDX1-dependent expression of tdtomato (PDX1-tom) in a subpopulation of sensory nerves. Many of these PDX1-tom afferents expressed the neurofilament 200 protein and projected to the skin. Tdtomato-labeled terminals were associated with hair follicles in the form of longitudinal and circumferential lanceolate endings suggesting a role in tactile and proprioceptive perception. To begin to examine the functional significance of PDX1 in afferents, we used Fura-2 imaging to examine calcium (Ca 2+ ) handling under naïve and nerve injury conditions. Neuropathic injury is associated with increased intracellular Ca 2+ signaling that in part results from dysregulation of the sarco/endoplasmic reticulum calcium transport ATPase (SERCA). Here we demonstrate that under naïve conditions, PDX1 regulates expression of the SERCA2B isoform in sensory neurons. In response to infraorbital nerve injury, a significant reduction of PDX1 and SERCA2B expression and dysregulation of Ca 2+ handling occurs in PDX1-tom trigeminal ganglia neurons. The identification of PDX1 expression in the somatosensory system and its regulation of SERCA2B and Ca 2+ handling provide a new mechanism to explain pathological changes in primary afferents that may contribute to pain associated with nerve injury.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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