Repurposed major urinary protein pheromones and adult sensory neurons: Roles in neuron plasticity and experimental diabetes

Am J Physiol Endocrinol Metab. 2022 May 30. doi: 10.1152/ajpendo.00001.2022. Online ahead of print.ABSTRACTMajor 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 (DRGs). 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 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 bound 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 behavioural abnormalities of experimental neuropathy. MUPs have actions beyond pheromone...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Source Type: research