Figure 1

The role of miR-21 in the long-lasting mechanical memory of MSCs in response to ectogenic tension. When MSCs cultured on stiff substrates, MRTF-A is induced to translocate to the nucleus where it binds to the CArG box to promote transcription of miR-21. High levels of miR-21 is maintained for a long term through unknown mechanisms. The persistent presence of miR-21 promotes the transcription of α-SMA and inhibits the transcription of antifibrogenic genes including Smad7, TGF-β receptor type III (TGF-bR III) and sprouty homolog 1 (SPRY1). Stiff-primed MSC memorizes their culture activation force and acquire fibrogenic capability in vivo. Conversely, when MSCs were cultured on soft substrates, the miR-21 level is kept low and thus reduce the profibrotic activity in vivo and allows better MSC-mediated tissue repair.