Gene expression profiling of Elastin (ELN) knock-down in human fibroblast MRC5. Gene expression profiling of Elastin (ELN) knock-down in human fibroblast MRC5

The ELN gene encodes tropoelastin which is used to generate elastic fibers that insure proper tissue elasticity. Decreased amounts of elastic fibers and/or accumulation of bioactive products of their cleavage, named elastokines, are thought to contribute to aging. Cellular senescence, characterized by a stable proliferation arrest and by the senescence-associated secretory phenotype (SASP), increases with aging. Here, we identified that decrease in ELN either by siRNA in normal human fibroblasts results in premature senescence. Surprisingly this effect is independent of elastic fiber degradation or elastokines production, but it relies on the rapid increase in HMOX1 after ELN downregulation. These results unveil a role for ELN in protecting cells from cellular senescence through a non-canonical mechanism. Overall design: Normal human fibroblast cells (MRC5) were transfected with siRNA against Elastin gene (siELN) or with scramble siRNA (siCTRL). Gene expression profiling was performed 1 day or 4 days after transfection. Three independent replicates have been performed.