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Table 2 Summary of studies evaluating BOO-induced molecular alterations and related cellular events in human detrusor

From: Progressive bladder remodeling due to bladder outlet obstruction: a systematic review of morphological and molecular evidences in humans

Author, year Experimental conditions Molecular alteration Cellular events
Backhaus, 2002 [34] HBSMCs exposed to HP (0.3, 20 and 40 cm H2O) for 1, 3, 7 and 24 h ↓ MMP-1, 2, 9 after exposure to 20 cm H2O for 7 h
↑TIMP-1 after exposure to 40 cm H2O 3, 7 and 24 h
 
Wang, 2013 [24] HBSMCs exposed to HP (0, 20, 40, 60, 80 and 100 cm H2O) for 6, 12, 24 and 72 h ↓expression of the gap junction connexin 43 under HP > 60 cm H2O for 24 h or HP > 40 cm H2O for 72 h.  
Chen, 2012 [28] HBSMCs exposed to CHP (0, 100, 200, and 300 cm H2O) ↑ SGK1 expression and activity ↑ proliferation in the 200 and 300 cm H2O groups
Chen, 2014 [32] HBSMCs exposed to CHP (0, 100, 200, and 300 cm H2O) ↑ Skp2 expression and ↓ p27 expression under 200 and 300 cmH2O CHP  
Wu, 2012 [31] HBSMCs exposed to CHP (static, 100, 200, and 300 cm H2O) Ras-related C3 botulinum toxin substrate 1, mitogen-activated protein kinase kinase 1/2 and extracellular regulated protein kinases 1/2 activated by 200 and 300 cmH2O CHP ↑proliferation under 200 and 300 cmH2O CHP
Preis, 2015 [27] HBSMCs exposed to HP of 136 cm H2O for 1 h ↑ expression of PDGFR α and β ↑ proliferation
Sun, 2016 [29] HBSMCs exposed to CHP up to 200 cm H2O ↑ miR-3180-5p ↑ proliferation
Sun, 2017 [30] HBSMCs exposed to CHP up to 200 cm H2O ↑ miR 4323 ↑ proliferation
Lee, 2006 [25] HBSMCs exposed to HP (40 cm H2O) and/or acetylcholine for 24 h Activation of muscarinic receptors ↑ proliferation
↑ hypertrophy
Lee, 2008 [26] HBSMCs exposed to acetylcholine in the presence or absence of HP (10, 20, and 40 cm H2O) ↑ M2 and M3 receptors expression ↑ proliferation
↑ hypertrophy
Yang, 2008 [23] HBSMCs exposed to cyclic stretch with maximum of 15% strain magnitude at a frequency of 0.3 Hz for either 1 h or 24 h. 30 genes upregulated and 59 downregulated after 1 h exposure
59 genes upregulated and 27 downregulated after 24 h exposure
 
Backhaus, 2002 [34] HBSMCs exposed to HP (0.3, 20 and 40 cm H2O) ↓ MMP-1, 2, 9
↑TIMP-1
 
Liang, 2017 [33] HBSMCs exposed to HP (100, 200, or 300 cm H2O) and/or acetylcholine ↑ IL-6, monocyte chemoattractant protein, and RANTES  
Galvin, 2004 [7] HBSMCs exposed to 1% O2tension for 24, 48, 72, and 96 h ↑ HIF-1α
↑ VEGF
↑ p27kip1
↓ proliferation
Wiafe, 2017 [35] HBSMCs exposed to 3% O2tension for 2, 24, 48, and 72 h ↑ HIF1α, HIF2α, and HIF3α
↑VEGF
↑TGFβ1
↑CTGF
↑ collagens 1, 2, 3, 4
↑ fibronectin
↑aggrecan
↑TIMP
↑ α-smooth muscle actin
↑vimentin,
↑desmin
↑TNFα, IL 1β, and IL 6
↓ IL-10
 
Boopathi , 2011 [38] Bladder samples from subjects with BOO and controls ↑ expression of GATA-6 in cases
↓ Caveolin-1 expression
 
Koritsiadis, 2008 [36] Bladder samples from subjects scheduled for BPE-surgery and controls ↑ HIF-1α expression in stromal cells between muscle bundles and in connective tissue beneath the mucosal layer  
Barbosa, 2017 [37] Bladder samples from subjects with obstructive BPE and controls ↑ collagens I and III
↓ MMP-9 and TIMP-1
↑VEGF
↓ CD105
 
Gheinani, 2017 [43] Bladder samples from subjects with different states of urodynamic defined BOO-induced bladder dysfunction Progressive increase in the number of altered mRNA and miRNAs from the detrusor overactive to the obstruction group to the underactive detrusor groups  
  1. BOO bladder outlet obstruction, BPE benign prostatic enlargement, CHP cyclic hydrodynamic pressure, CTGF connective tissue transforming growth factor, HBSMCs human bladder smooth muscle cells, HIF hypoxia inducible factor, HP hydrostatic pressures, IL interleukin, MMP matrix metalloproteinases, PDGFR platelet derived growth factor receptor, SGK1 serum-glucocorticoid regulated kinase 1, Skp2 S-phase kinase-associated protein 2, TGF transforming growth factor, TIMP tissue inhibitor of metalloproteinases, TNF tumor necrosis factor, VEGF vascular endothelial growth factor