design: Total RNA was extracted from in vitro cultured fibroblasts using TRI Reagent (T9424, Sigma) according to the manufacturers instruction. After treatments, cells were washed with sterile PBS, and 333 l of TRI reagent was poured into each well of 6-well cell culture plates. Since each experiment was performed in 3 technical replicates, the total volume for each biological replicate was 1 ml of TRI Reagent. Then, cells were scrapped using a 1ml pipette tip. Subsequently, cell suspension in TRI reagent was transferred into 1.5 ml tubes and stored at -80 until RNA extraction. At the day of isolation TRI reagent mixtures were incubated 5 minutes at room temperature. Then, the mixture was pipetted several times, and 200 l of chloroform (234430111, POCH) was added to each tube. The tubes were inverted several times to mix the contents, incubated for 5 minutes at room temperature and centrifuged for 15 minutes at 4, 12.000  g. After centrifugation, the upper (aqueous) phase, containing RNA, was transferred into new collection tube, and mixed with 500 l of isopropanol (751500111, POCH), and incubated for 15 minutes on ice. Then, tubes were centrifuged for 10 minutes at 4, 12.000  g. After centrifugation, the supernatant was discarded and the pellet was washed twice with 1 ml of 75% ethanol and centrifuged at 4 for 6 minutes at 8.000  g. After second centrifugation, the supernatant was discarded and the pellet was dried in inverted tubes placed on paper towels for 15-30 minutes. Then, the pellet was suspended in 50 l of nuclease-free water. The concentration and quality of total RNA was determined spectrophotometrically using DeNovix Spectrofotometer. The ratio of absorbance at 260 and 280 nm (A260/280) was approximately 2. Moreover, RNA integrity number (RIN), which is a measure of the integrity and level of degradation of an RNA sample was assessed for each RNA isolate using Agilent 2100 system and Expert software (Agilent Technologies, Inc., Santa Clara, CA, USA). All samples had RIN approximately 10 and were processed further. The isolated RNA was stored at -80 for further analysis.