DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy
Bradley S. Ferguson, Sara A. Wennersten, Kimberly Demos-Davies, Marcello Rubino, Emma Robinson, Maria A. Cavasin, Matthew S. Stratton, Andrew M. Kidger, Tianjing Hu, Stephen M. Keyse, Robert A. McKnight, Robert H. Lane, Eva Nozik‐Grayck, Mary C.M. Weiser‐Evans, Timothy A. McKinsey
Abstract
Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response to angiotensin II infusion, mice lacking DUSP5 develop pulmonary hypertension and right ventricular cardiac hypertrophy. These findings illustrate DUSP5-mediated suppression of ERK signaling in the lungs as a protective mechanism.