Citation Spotlight: Stimulation of Fibronectin Matrix Assembly by Lysine Acetylation

Schematic representation of acetylated integrin interacting with ECM

Vega et al. recently identified a regulatory lysine acetylation mechanism that controls extracellular matrix (ECM) assembly and production in mesangial cells.  One of the major complications of diabetes is diabetic nephropathy, with fibrosis being a hallmark of the disease.  Excess deposition of ECM, produced by mesangial cells, occurs in the glomeruli. Fibronectin (FN), a major component of the mesangial ECM, is an abundant and ubiquitous ECM protein important for interactions between cells and the surrounding matrix.  Vega et al. investigated the effects of acetylation on FN assembly and identified acetylated β1 integrin as a mediator of cell-FN interactions and downstream FN matrix assembly. As a first step, deacetylase inhibitors were used to treat mesangial cells, which increased acetylation as well as FN matrix assembly. Deacetylase inhibitor treatment promoted endogenous acetylation of β1 integrin in this model, a key piece of evidence describing physiological regulation. Molecular studies using β1 integrin acetylation mimetics were utilized to characterize its role in FN matrix effects, which resulted in the acetylated mimetic promoting enhanced FN matrix assembly.  Interestingly, the investigators saw further increases in FN matrix in WT as well as in β1 integrin mimetics when stimulated with deacetylase inhibitors indicating a role for other acetylated proteins in FN assembly, which was supported by the large number of acetylated proteins identified by pull down.  Identifying endogenous levels of acetylated β1 integrin was achieved using Cytoskeleton’s Acetyl-Lysine Detection Kit, and these finding provided essential information towards their overall finding that lysine acetylation provides a mechanism for glucose-induced fibrosis by up-regulation of FN matrix assembly.

Schematic representation of acetylated integrin interacting with ECM

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