2. Academic Validation
  3. β-Adrenoceptor Signaling Activation Improves Bladder Fibrosis by Inhibiting Extracellular Matrix Deposition of Bladder Outlet Obstruction

β-Adrenoceptor Signaling Activation Improves Bladder Fibrosis by Inhibiting Extracellular Matrix Deposition of Bladder Outlet Obstruction

  • Front Biosci (Landmark Ed). 2024 Sep 24;29(9):336. doi: 10.31083/j.fbl2909336.
Junyu Lai 1,  Guo Chen 2 3,  Hongwei Su 1,  Qing He 4,  Kaiwen Xiao 2,  Banghua Liao 2,  Jianzhong Ai 2
Affiliations

Affiliations

  • 1 Department of Urology, The Affiliated TCM Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China.
  • 2 Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.
  • 3 Department of Urology, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.
  • 4 Department of Urology, The Third People's Hospital of Chengdu, Southwest Jiaotong University, 610043 Chengdu, Sichuan, China.
PMID: 39344310 DOI: 10.31083/j.fbl2909336
Abstract

Background: Partial bladder outlet obstruction (pBOO) causes deposition of extracellular matrix (ECM), promotes bladder fibrosis, and decreases bladder compliance.

Methods: To investigate the effect of β-adrenoceptor (ADRB) on the ECM deposition of pBOO rat model and explore its underlying mechanism, human bladder smooth muscle cells (hBSMCs) were exposed to the pathological hydrostatic pressure (100 cm H2O) for 6 h, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were employed. Then the rats of sham operation and pBOO model were treated with vehicle or ADRB agonists for 3 weeks, and the alterations of the bladder were observed via Masson staining and immunohistochemical analysis.

Results: 100 cm H2O hydrostatic pressure significantly upregulated the expression of collagen I (COL1), collagen III (COL3) and fibronectin (FN), and downregulated the expression of ADRB2 and ADRB3 of hBSMCs at 6 h. The agonists of ADRB2 and ADRB3, Formoterol and BRL 37344, decreased COL1 and FN expression of hBSMCs under 100 cm H2O for 6 h compared with the cells exposed to hydrostatic pressure only. As the classic downstream pathways of ADRB, the EPAC pathway inhibited COL1 and FN expression of hBSMCs via regulating SMAD3 and SMAD2 activities, respectively. In pBOO rats, Procaterol (ADRB2 agonist), and Mirabegron (ADRB3 agonist) inhibited the formation of collagen and decreased the expression of FN and COL1 in the bladders of pBOO rats.

Conclusions: The bladder fibrosis of pBOO and deposition of hBSMCs ECM under hydrostatic pressure were regulated by ADRB2, and ADRB3 via EPAC/SMAD2/FN and EPAC/SMAD3/COL1 pathways, these findings pave an avenue for effective treatment of pBOO.

Keywords

ECM; hBSMCs; pBOO; pathological hydrostatic pressure; β-adrenoceptor.

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