High-Content Screens Are Essential To Identify Secreted Factors Relevant To Biological Processes

The authors of this study identify DNA damage signaling as a key mediator of vascular smooth muscle cell (VSMC) osteogenic differentiation in a model of calcification and aging. They demonstrate that the accumulation of prelamin A, a nuclear lamin protein that plays an important role in VSMC calcification, interferes with DNA damage repair signaling which leads to premature cell senescence and accelerated calcification. Cytokine array analysis identified several ataxia-telangiectasia mutated-dependent senescence-associated secretory phenotype factors/cytokines released by prelamin A–positive VSMCs, including calcification regulators bone morphogenetic protein 2, osteoprotegerin, and interleukin 6, which may drive calcification both locally and at remote sites.

Liu, Y., Drozdov, I., Shroff, R., Beltran, L. E., & Shanahan, C. M. (2013). Prelamin A accelerates vascular calcification via activation of the DNA damage response and senescence associated secretory phenotype in vascular smooth muscle cells. Circulation research, CIRCRESAHA-112.

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