Effect of QSKL on MAPK and RhoA Pathways in a Rat Model of Heart Failure

Figure 10

Antifibrosis mechanisms of QSKL on the RhoA/ROCK and MAPK pathways. The RhoA/ROCK and MAPK pathways contribute to fibrosis by promoting the migration and proliferation of fibroblasts. During the fibrotic process, Ang II combines with AT-1R, which can interact with G-proteins such as RhoA. After receiving a signal from AT-1R, RhoA will activate the target proteins, such as ROCK1 and ROCK2, which in turn phosphorylate MLC and enhance the cytoplasmic division during fibroblast proliferation. Meanwhile, MLC promotes cell migration by accelerating the turnover of focal adhesion plaques. RhoA can also activate the raf protein on the upper stream of the MAPK signaling pathway. Activated raf stimulates MEK which then phosphorylates the ERK and JNK proteins. Phosphorylated ERK and JNK activate certain transcription factors that translocate into the nucleus and stimulate fibroblast proliferation. QSKL inhibits the proliferation and migration of the fibroblasts by acting on the key molecules in the RhoA/ROCK and MAPK signaling pathways, thereby exerting antifibrosis effects.