“…Since the inflammatory pathway is already known to be fibrosis inducing (23, 36), we speculate that the mechanism of "stiffening" of the ECM is mediated through these inflammatory pathways. Importantly, this type of response would provide a negative feedback loop in that, after stiffening, the ECM would prevent excessive fiber strain, which is believed to be related to muscle fiber injury (2,30,31), which would then relieve the inflammatory stimulus and stabilize the ECM system. Of course, this suggested mechanism is speculative at this point but can be experimentally tested.…”