Figure 8. Scheme of adaptive MSC responses to different environmental TGF‐β1 levels.

1. In the environment with low concentrations of TGF‐β1, activation of TGF‐β receptor induces miR‐21, which blocks the translation of Smad7, thus relieves the suppression of TGF‐β1 expression by Smad7, and promotes TGF‐β1 release from MSCs.
2. Overactivation of TGF‐β receptor in MSCs by high environmental TGF‐β1 down‐regulates miR‐21 and thus no longer inhibits Smad7 translation and leads to close the TGF‐β1 signal circuit. Such adaptive response is disturbed by deliberately changing the expression of components in the signaling pathway, such as (1) silencing TGF‐β1 expression in MSCs by TGF‐β1 siRNA, (2) blocking TGF‐β receptor activity by chemical inhibitor SB431542, (3) silencing Smad7 expression by Smad7 siRNA, (4) overexpression of miR‐21 by miR‐21 mimic, and (5) knockdown miR‐21 by miR‐21 inhibitor.