The study was done to investigate whether PDE5is and SERMs can reverse transforming growth factor beta 1 (TGF-β1)–induced myofibroblast transformation and determine the point of no return.

Vardenafil or tamoxifen did not prove effective to reverse the myofibroblast traits of alpha-smooth muscle actin expression and extracellular matrix production, tamoxifen only affected collagen contraction after 72 hours of TGF-β1 treatment. 5A and (ER)-β were downregulated after 72 hours, and estrogen receptor -α protein could not be quantified. Tamoxifen could prevent myofibroblast transformation until 36 hours after TGF-β1 treatment, whereas vardenafil could prevent only 1 day after TGF-β1 treatment. The antifibrotic signaling pathways, peroxisome proliferator-activated receptor gamma and betaglycan (TGFB receptor III), were significantly downregulated after 36 hours of TGF-β1 exposure. Using PDE5is and SERMs only help for early-phase PD.

The study concluded that the use of primary human TA-derived fibroblasts that enhance translatability of the results. It demonstrated timing for administration of drugs affecting myofibroblast transformation appears to be vital in in vitro models of PD, where 36 hours of TGF-β1 treatment can be suggested as a “point of no return” for myofibroblast transformation.