Table 1. In vivo studies in PD utilizing TGF-β1 stimulation model.
| Authors | Year | Cell species | Type of TA | Compound investigated | Timing of administration | Outcomes |
|---|---|---|---|---|---|---|
| Target-based approach | ||||||
| Piao et al. | 2010 | Human | Both PD and normal TA samples | SKI2162; small-molecule inhibitor of activin receptor-like kinase 5 (ALK5), a type I receptor of TGF-β | Pretreatment with compound | Inhibition of phosphorylation Smad2/3; inhibition ECM production (protein) |
| Shindel et al./Lin et al. | 2010 | Human | Both PD and normal TA samples | Pentoxifylline | Pretreatment with compound | Inhibition of collagen fiber deposition and elastogenesis |
| Jung et al. | 2013 | Human | PD samples | HS-173; novel inhibitor of phosphoinositide 3-kinase (PI3K)/Akt | Co-stimulation (compound + TGF-β1) | Reduction of α-SMA, vimentin, plasminogen activator inhibitor-1 (PAI-1), fibronectin, collagen I/IV and Smad2/3; inhibition of PI3K/Akt by impeding Akt, mTOR and P70S6K |
| Ryu et al. | 2013 | Human | PD samples | small interfering RNA (siRNA)-mediated silencing of histone deacetylase 2 (HDAC2) | Pretreatment with compound | Inhibition FB>MFB; inhibition of phosphorylation and nuclear translocation of Smad2/3 |
| Jiang et al. | 2015 | Sprague-Dawley rats | Normal TA samples | estrogen [17β-estradiol (E2)] | Co-stimulation (compound + TGF-β1) | Inhibition of α-SMA expression, concentration of hydroxyproline (collagen marker) and cellular contraction |
| Choi et al. | 2015 | Human | PD samples | Smad7 gene overexpression | Pretreatment with compound | inhibition of phosphorylation and nuclear translocation of SMAD2/3, MFB transformation, and production of ECM |
| Mateus et al. | 2018 | Human | Both PD and normal TA samples | BAY 60-6583 (ADORA2B agonist) | Co-stimulation (compound + TGF-β1) | Inhibition of FB > MFB |
| Milenkovic et al. | 2019 | Human | PD samples | Simvastatin a Y-27632 (ROCK-inhibitor) | Co-stimulation (compound + TGF-β1) | Inhibition of FB > MFB, inhibition of α-SMA, collagen I/III, elastin, CTGF (mRNA) and impairment of ROCK-signalling through prevention of YAP/TAZ nuclear transformation |
| Phenotypic-based approach | ||||||
| Jiang et al. | 2017 | Sprague-Dawley rats | Normal TA samples | Adipose-derived stem cells (ADSC) | ADSC administration after MFB transformation | Inhibition of expression of α-SMA and collagen I in MFBs; Reduction in phosphorylation and activity of Smad2, RhoA, ROCK1/2 and an upregulation of MMPs and caspases |
| Ilg et al. | 2019 | Human | Both PD and normal TA samples | Tamoxifen and Vardenafil (separately and in combination) | Co-stimulation (compound + TGF-β1) | Inhibition of MFB transformation, cellular contraction, and ECM production |
TA, tunica albuginea; PD, Peyronie’s disease; ADSC, adipose-derived stem cell; ECM, extracellular matrix; MMP, matrix metalloprotease; FB, fibroblast; MFB, myofibroblast; CTGF, connective tissue growth factor.