Loss of cathepsin C enhances keratinocyte proliferation and inhibits apoptosis  

作　　者：Xin Li Ling-Fei Jia Yunfei Zheng Yiping Huang Man Qin Yuan Yang 

机构地区：[1]Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology [2]Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology [3]Central Laboratory, Peking University School and Hospital of Stomatology [4]Department of Orthodontics, Peking University School and Hospital of Stomatology

出　　处：《Science Bulletin》2016年第14期1107-1114,共8页科学通报（英文版）

摘　　要：Papillon-Lefevre Syndrome is a rare autosomal recessive disorder characterized by rapidly progressive periodontitis and confined palrnoplantar 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）-I, but not KRT9, was correlated with CTSC expression. Loricrin was increased in the CTSC-overex- pression 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.Papillon–Lefe`vre 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. Ha Ca T keratinocytes were transfected with wild-type CTSC and CTSC-targeted si RNAs 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 Ha Ca T 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 Ha Ca T cells. This study suggested that loss of CTSC contributes to keratinocyte hyperkeratosis via downregulation of loricrin and enhanced cell proliferation.

关 键 词：Papillon-Lefevre syndrome CathepsinC LORICRIN Cytokeratin 1 - Cytokeratin 9 

分 类 号：R596[医药卫生—内科学]