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Loss of cathepsin C enhances keratinocyte proliferation and inhibits apoptosis

  • Article
  • Life & Medical Sciences
  • Published:
Science Bulletin

Abstract

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.

摘要

牙周破坏掌跖角化综合征是一种常染色体隐性遗传疾病, 其特点是快速进展的牙周炎和掌跖皮肤局限性角化。本研究检测了下调组织蛋白酶C (CTSC) 所引起的角蛋白-1、9和兜甲蛋白在mRNA、蛋白水平表达的变化, 以及对细胞增殖和凋亡的影响。结果表明CTSC过表达时兜甲蛋白表达上调, 同时促进细胞凋亡; CTSC基因沉默后, 兜甲蛋白表达下调, 抑制细胞凋亡, 促进细胞增殖。本研究对了解牙周破坏掌跖角化综合征的致病机制提供了进一步线索。

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Author notes

    Authors and Affiliations

    1. Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, China

      Xin Li, Man Qin & Yuan Yang

    2. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, China

      Ling-Fei Jia & Yunfei Zheng

    3. Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, China

      Ling-Fei Jia

    4. Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China

      Yiping Huang

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    1. Xin Li
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    2. Ling-Fei Jia
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    3. Yunfei Zheng
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    5. Man Qin
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    Correspondence to Yuan Yang.

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    Xin Li and Ling-Fei Jia contributed equally to this work.

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    Cite this article

    Li, X., Jia, LF., Zheng, Y. et al. Loss of cathepsin C enhances keratinocyte proliferation and inhibits apoptosis. Sci. Bull. 61, 1107–1114 (2016). https://doi.org/10.1007/s11434-016-1085-z

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    • DOI: https://doi.org/10.1007/s11434-016-1085-z

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