RNAseq of uPA (PLAU) knockdown in human corneal fibroblasts

Scarring and fibrotic disease result from the persistence of myofibroblasts characterized by high surface expression of αv integrins and subsequent activation of TGFβ, however the mechanism controlling their surface abundance is unknown. We previously found that knockdown of uPA (urokinase plasminogen activator) in primary human corneal fibroblasts generated myofibroblasts with cell surface accumulation of integrin αvβ5 (Wang et al., 2012,
PMID: 22470492). Genetic screening of these myofibroblasts was pursued to test for changes in the gene expression of degradation machinery (ligases or deubiquitinases) that could effect cell surface expression of integrins. We found that a subset of human deubiquitinases were increased in these myofibroblasts. Secondary screening revealed that the deubiquitinase USP10 regulates alpha v integrin protein expression.