Insight into SLC9A3 deficiency-mediated micturition dysfunction caused by electrolyte imbalance.

Kuo-Chiang Chen, Meng-Lin Chang, Chun-Sian Lin, Chellappan Praveen Rajneesh, Chun-Hou Liao, Wen-Chen You, Hung-Chune Maa, Yi-No Wu

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2023 Feb

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Solute carrier family nine isoform 3 (SLC9A3) is an Na+/H+ exchanger that regulates Ca2+ homeostasis. SLC9A3 is largely involved in the transepithelial absorption of Na+/H+ and frequently functions in pair with a Cl-/HCO3- exchanger. To investigate the impact and pathophysiological mechanisms of long-term SLC9A3 deficiency on lower urinary tract symptoms (LUTS) in a mouse model MATERIALS AND METHODS: Slc9a3 knockout and wild-type mice (average >6 months) were used. The effects of SLC9A3 depletion on bladder and urethral functions and effectiveness of voiding were assessed using a cystometrogram (CMG). Histology, blood electrolytes, and gene expression were also analyzed. The SLC9A3-deficient mice had smaller gross bladders than the wild-type mice. The CMG analysis revealed normal peak micturition pressure, higher threshold pressure, short intercontraction interval, less voided volume, and poor compliance in the SLC9A3-deficient mice, similar to clinical LUTS. Histological analysis revealed loose detrusor muscle and loss of transformability of the urothelium in the SLC9A3-deficient mice. Masson's trichrome analysis revealed severe collagen deposition in the detrusor muscle. Immunofluorescence staining also demonstrated a significant decrease in cytokeratins 5 and 20. Gene and protein expression analyses confirmed that SLC9A3 does not act directly on bladder tissue. Homeostasis was correlated with bladder dysfunction in the SLC9A3-deficient mice. Fibrosis and collagen deposition in the bladder of the SLC9A3-deficient mice is due to bladder inflammation because of decreased blood flow and deregulated systemic homeostasis. Long-term SLC9A3 depletion causes progressive bladder dysfunction, similar to human LUTS. Electrolyte imbalance causes SLC9A3 deficiency-mediated progressive micturition dysfunction. Copyright © 2023. Published by Elsevier Masson SAS.

Citation

Kuo-Chiang Chen, Meng-Lin Chang, Chun-Sian Lin, Chellappan Praveen Rajneesh, Chun-Hou Liao, Wen-Chen You, Hung-Chune Maa, Yi-No Wu. Insight into SLC9A3 deficiency-mediated micturition dysfunction caused by electrolyte imbalance. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023 Feb;158:114155