RESEARCH Megakaryoblastic leukemi

Fibrosing disorders of the lung, such as idiopathic pulmonary fibrosis, are characterized by progressive extracellular matrix accumulation that is driven by myofibroblasts [1-4]. We have previously reported that myofibroblast differentiation requires signaling via the transcription factors megakaryoblastic leukemia-1 (MKL1) and serum response factor (SRF) [5-7]. MKL1 is regulated by the actin cytoskeleton [4], and activates the transcription factor SRF [8-10]. Additionally, MKL1 has been observed to be required for myofibroblast differentiation in response to mechanical signals, matrix stiffness, and profibrotic G-protein coupled receptor agonists [11-13]. Furthermore, our group has observed that signaling via protein kinase A (PKA) can protect against bleomycin-induced pulmonary fibrosis in mice, and that this protective effect is likely vi