The University of Southampton
University of Southampton Institutional Repository

The cystatin M/E-cathepsin L balance is essential for tissue homeostasis in epidermis, hair follicles, and cornea

Zeeuwen, Patrick L.J.M., van Vlijmen-Willems, Ivonne M.J.J., Cheng, Tsing, Rodijk-Olthuis, Diana, Hitomi, Kiyotaka, Hara-Nishimura, Ikuko, John, Susan, Smyth, Neil, Reinheckel, Thomas, Hendriks, Wiljan J.A.J. and Schalkwijk, Joost (2010) The cystatin M/E-cathepsin L balance is essential for tissue homeostasis in epidermis, hair follicles, and cornea The FASEB Journal (doi:10.1096/fj.10-155879).

Record type: Article

Abstract

Cystatin M/E (CST6) is a nonredundant, epithelium-specific protease inhibitor with a presumed role in epidermal differentiation and tumor suppression. We have previously reported that cystatin M/E deficiency in Cst6(-)(/)(-) mice causes neonatal lethality because of excessive transepidermal water loss. Biochemical evidence suggests that cystatin M/E controls the activity of legumain, cathepsin L, cathepsin V, and transglutaminase-3. Using a genetic approach we sought to define the role of cystatin M/E in epithelial biology by identification of its target proteases and their downstream functions. Ablation of cathepsin L in a Cst6(-)(/)(-) background (Cst6(-)(/)(-)Ctsl(-)(/)(-) double-knockout mice) restored viability and resulted in normalization of stratum corneum morphology. Ablation of legumain or transglutaminase-3 in Cst6(-)(/)(-) mice, however, did not rescue the lethal phenotype. Intriguingly, both Cst6(-)(/)(-)Ctsl(-)(/)(-) and Cst6(-)(/)(-)Ctsl(+)(/)(-) mice were viable, but the absence of cystatin M/E caused scarring alopecia in adult animals. In the cornea of Cst6(-)(/)(-)Ctsl(+)(/)(-) mice, we observed keratitis, hyperplasia, and transition to a cornified epithelium. Evidence is provided that activation of cathepsin D and transglutaminase-1 are downstream events, dependent of cathepsin L activity. We conclude that a tightly regulated balance between cathepsin L and cystatin M/E is essential for tissue integrity in epidermis, hair follicles, and corneal epithelium.-Zeeuwen, P.L.J.M., van Vlijmen-Willems, I.M.J.J., Cheng, T., Rodijk-Olthuis, D., Hitomi, K., Hara-Nishimura, I., John, S., Smyth, N., Reinheckel, T., Hendriks, W.J.A.J., Schalkwijk, J. The cystatin M/E-cathepsin L balance is essential for tissue homeostasis in epidermis, hair follicles and cornea.

Full text not available from this repository.

More information

Published date: 21 May 2010
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 159373
URI: http://eprints.soton.ac.uk/id/eprint/159373
ISSN: 0892-6638
PURE UUID: 6ecb6b16-09e4-4910-9bdf-7c3400413451

Catalogue record

Date deposited: 30 Jun 2010 08:29
Last modified: 18 Jul 2017 12:37

Export record

Altmetrics

Contributors

Author: Patrick L.J.M. Zeeuwen
Author: Ivonne M.J.J. van Vlijmen-Willems
Author: Tsing Cheng
Author: Diana Rodijk-Olthuis
Author: Kiyotaka Hitomi
Author: Ikuko Hara-Nishimura
Author: Susan John
Author: Neil Smyth
Author: Thomas Reinheckel
Author: Wiljan J.A.J. Hendriks
Author: Joost Schalkwijk

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×