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Am J Physiol Endocrinol Metab

Title:		Repurposed major urinary protein pheromones and adult sensory neurons: roles in neuron plasticity and experimental diabetes
Author(s):		Poitras T; Singh V; Piragasam RS; Wang X; Mannaa AM; Chandrasekhar A; Martinez J; Fahlman R; Zochodne DW;
Address:		"Division of Neurology, Department of Medicine and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada. Division of Neurology, Department of Clinical Neuroscience and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada. Southern Alberta Microarray Facility, Department Biochemistry and Molecular. Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. Department of Oncology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. INSERM U1192, Laboratoire Proteomique, Reponse Inflammatoire & Spectrometrie de Masse (PRISM), Universite de Lille, Lille, France. Higher Institute of Engineering and Technology, New Borg El-Arab City, Egypt"
Journal Title:		Am J Physiol Endocrinol Metab
Year:		2022
Volume:		20220530
Issue:		1
Page Number:		E53 - E68
DOI:		10.1152/ajpendo.00001.2022
ISSN/ISBN:		1522-1555 (Electronic) 0193-1849 (Linking)
Abstract:		"Major urinary proteins (MUPs), members of the broader lipocalin protein family, are classified as pheromones that are excreted in male rodent urine to define conspecific territoriality. In screening for differentially regulated mRNA transcripts in a mouse model of type 1 experimental diabetes mellitus (DM), we identified an unexpected upregulation of several closely related MUP transcripts within diabetic sensory dorsal root ganglia (DRG). Both sexes expressed overall MUP protein content as identified by an antibody widely targeting these upregulated family members, and immunohistochemistry identified expression within neurons, satellite glial cells, and Schwann cells. In dissociated adult sensory neurons, knockdown by an siRNA targeting upregulated MUP mRNAs, enhanced neurite outgrowth, indicating a growth-suppressive role, an impact that was synergistic with subnanomolar insulin neuronal signaling. While MUP knockdown did not generate rises in insulin signaling transcripts, the protein did bind to several mitochondrial and glial targets in DRG lysates. Analysis of a protein closely related to MUPs but that is expressed in humans, lipocalin-2, also suppressed growth, but its impact was unrelated to insulin. In a model of chronic type 1 DM, MUP siRNA knockdown improved electrophysiological and behavioral abnormalities of experimental neuropathy. MUPs have actions beyond pheromone signaling in rodents that involve suppression of growth plasticity of sensory neurons. Its hitherto unanticipated actions overlap with those of lipocalin-2 and may identify a common and widely mediated impact on neuron growth properties by members of the lipocalin family. Knockdown of MUP supports the trophic actions of insulin as a strategy that may improve features of type 1 experimental diabetic neuropathy.NEW & NOTEWORTHY New molecular mechanisms are important to unravel and understand diabetic polyneuropathy, a disorder prevalent in over half of persons with diabetes mellitus (DM). MUPs, members of the lipocalin family of molecules, have an unexpected impact on the plasticity of sensory neurons that are targeted in type 1 experimental diabetic neuropathy. This work explores this potential target in neuropathy in the context of the lipocalin family of molecules"
Keywords:		"Animals *Diabetes Mellitus, Experimental/genetics/metabolism *Diabetes Mellitus, Type 1/metabolism *Diabetic Neuropathies Female Ganglia, Spinal/metabolism Humans Insulin/metabolism Lipocalin-2 Male Mice Pheromones/metabolism Proteins RNA, Small Interferi;Neuroscience;"
Notes:		"MedlinePoitras, Trevor Singh, Vandana Piragasam, Ramanaguru S Wang, Xiuling Mannaa, Atef M Chandrasekhar, Ambika Martinez, Jose Fahlman, Richard Zochodne, Douglas W eng FRN15686/CIHR/Canada Research Support, Non-U.S. Gov't 2022/06/01 Am J Physiol Endocrinol Metab. 2022 Jul 1; 323(1):E53-E68. doi: 10.1152/ajpendo.00001.2022. Epub 2022 May 30"