Loss of cathepsin C enhances keratinocyte proliferation and inhibits apoptosis

Papillon-Lefèvre Syndrome is a rare autosomal recessive disorder characterized by rapidly progressive periodontitis and confined palmoplantar hyperkeratosis resulting from genetic mutations in cathepsin C (CTSC). The present study investigated the effect of CTSC on keratinocyte proliferation and apoptosis. HaCaT keratinocytes were transfected with wild-type CTSC and CTSC-targeted siRNAs to investigate the effects of CTSC expression on cell keratosis. Real-time PCR and Western blot analyses showed that the levels of loricrin and keratin (KRT)-1, but not KRT9, was correlated with CTSC expression. Loricrin was increased in the CTSC-overexpression group and downregulated in the CTSC-silenced group. A positive association between loricrin expression and cell apoptosis was detected in HaCaT keratinocytes. KRT1 was decreased in the CTSC-overexpression group and increased in the CTSC-silenced group. Prominent, punctuate KRT1 aggregates were present in CTSC-knockdown HaCaT cells. This study suggested that loss of CTSC contributes to keratinocyte hyperkeratosis via downregulation of loricrin and enhanced cell proliferation.