Intracellular and extracellular DKK-3 play crucial roles in preventing cardiac hypertrophy [63] and promote the differentiation of stem cells into vascular smooth muscle cells [41], via the activation of several intracellular signaling pathways, including the ASK1/JNK/p38 [apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38] and MEK/ERK/ATF6 axes, respectively (Figure 3B,C). This evidence concerns the gene MAP3K5 and cardiac hypertrophy.