Journal of Molecular Medicine

, Volume 87, Issue 3, pp 249–260

Lysosomal cysteine peptidase cathepsin L protects against cardiac hypertrophy through blocking AKT/GSK3β signaling

  • Qizhu Tang
  • Jun Cai
  • Difei Shen
  • Zhouyan Bian
  • Ling Yan
  • You-Xin Wang
  • Jie Lan
  • Guo-Qing Zhuang
  • Wen-Zhan Ma
  • Wei Wang
Original Article

DOI: 10.1007/s00109-008-0423-2

Cite this article as:
Tang, Q., Cai, J., Shen, D. et al. J Mol Med (2009) 87: 249. doi:10.1007/s00109-008-0423-2

Abstract

The lysosomal cysteine peptidase cathepsin L (CTSL) is an important lysosomal proteinase involved in a variety of cellular functions including intracellular protein turnover, epidermal homeostasis, and hair development. Deficiency of CTSL in mice results in a progressive dilated cardiomyopathy. In the present study, we tested the hypothesis that cardiac overexpression of human CTSL in the murine heart would protect against cardiac hypertrophy in vivo. The effects of constitutive human CTSL expression on cardiac hypertrophy were investigated using in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding (AB) in CTSL transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathological analyses of heart samples. Constitutive overexpression of human CTSL in the murine heart attenuated the hypertrophic response, markedly reduced apoptosis, and fibrosis. Cardiac function was also preserved in hearts with increased CTSL levels in response to hypertrophic stimuli. These beneficial effects were associated with attenuation of the Akt/GSK3β signaling cascade. Our in vitro studies further confirmed that CTSL expression in cardiomyocytes blunts cardiac hypertrophy through blocking of Akt/GSK3β signaling. The study indicates that CTSL improves cardiac function and inhibits cardiac hypertrophy, inflammation, and fibrosis through blocking Akt/GSK3β signaling.

Keywords

Cathepsin Lcardiac remodelingAKTFibrosisGSK3β

Supplementary material

109_2008_423_MOESM1_ESM.pdf (1.3 mb)
ESM Fig. 1 (PDF 1.31 MB)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Qizhu Tang
    • 1
  • Jun Cai
    • 2
    • 3
  • Difei Shen
    • 1
  • Zhouyan Bian
    • 1
  • Ling Yan
    • 1
  • You-Xin Wang
    • 4
    • 5
  • Jie Lan
    • 4
    • 5
  • Guo-Qing Zhuang
    • 4
    • 5
  • Wen-Zhan Ma
    • 4
    • 5
  • Wei Wang
    • 4
    • 5
  1. 1.Cardiovascular Research Institute of Wuhan University and Department of CardiologyRenmin Hospital of Wuhan UniversityWuhanPeople’s Republic of China
  2. 2.Cardiovascular Research CenterMassachusettes General Hospital, Harvard Medical SchoolCharlestownUSA
  3. 3.Department of Cardiology, Beijing Chaoyang HospitalCapital Medical UniversityBeijingPeople’s Republic of China
  4. 4.Graduate School of Chinese Academy of SciencesBeijingPeople’s Republic of China
  5. 5.School of Public Health and Family MedicineCapital Medical UniversityBeijingPeople’s Republic of China