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

Autor: Chen KC; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan; Department of Urology, Cathay General Hospital, Taipei City 106438, Taiwan., Chang ML; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan; Department of Urology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City 243089, Taiwan., Lin CS; Graduate Institute of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan., Rajneesh CP; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan., Liao CH; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan; Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City 231403, Taiwan., You WC; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan., Maa HC; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan; Department of Pathology, Cardinal Tien Hospital, New Taipei City 231403, Taiwan. Electronic address: a1959480613@gmail.com., Wu YN; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan. Electronic address: 133838@mail.fju.edu.tw.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Feb; Vol. 158, pp. 114155. Date of Electronic Publication: 2023 Jan 03.
DOI: 10.1016/j.biopha.2022.114155
Abstrakt: Background: Solute carrier family nine isoform 3 (SLC9A3) is an Na + /H + exchanger that regulates Ca 2 + homeostasis. SLC9A3 is largely involved in the transepithelial absorption of Na + /H + and frequently functions in pair with a Cl - /HCO3 - exchanger.
Objective: 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.
Results: 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.
Discussion: 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.
Conclusion: Electrolyte imbalance causes SLC9A3 deficiency-mediated progressive micturition dysfunction.
Competing Interests: Conflict of interest statement The authors report no conflicts of interest.
(Copyright © 2023. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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