Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec;144(6):1338-1349.
doi: 10.1097/PRS.0000000000006275.

Expression of Cathepsins B, D, and G by the Embryonic Stem Cell-Like Population within Human Keloid Tissues and Keloid-Derived Primary Cell Lines

Claudia Paterson  1 , Valerie M Y Lee  1 , Helen D Brasch  1 , Bede van Schaijik  1 , Reginald Marsh  1 , Swee T Tan  1 , Tinte Itinteang  1
Affiliations

Expression of Cathepsins B, D, and G by the Embryonic Stem Cell-Like Population within Human Keloid Tissues and Keloid-Derived Primary Cell Lines

Claudia Paterson et al. Plast Reconstr Surg. 2019 Dec.

Abstract

Background: The authors have previously shown that an embryonic stem cell-like population within keloid-associated lymphoid tissues in keloid lesions expresses components of the renin-angiotensin system that may be dysregulated. The authors hypothesized that cathepsins B, D, and G are present within the embryonic stem cell-like population in keloid lesions and contribute to bypass loops of the renin-angiotensin system.

Methods: 3,3'-Diaminobenzidine immunohistochemical staining for cathepsins B, D, and G was performed on formalin-fixed paraffin-embedded sections in keloid tissue samples of 11 patients. Immunofluorescence immunohistochemical staining was performed on three of these keloid tissue samples, by co-staining with CD34, tryptase, and OCT4. Western blotting, reverse transcription quantitative polymerase chain reaction, and enzyme activity assays were performed on five keloid tissue samples and four keloid-derived primary cell lines to investigate protein and mRNA expression, and functional activity, respectively.

Results: 3,3'-Diaminobenzidine immunohistochemical staining demonstrated expression of cathepsins B, D, and G in all 15 keloid tissue samples. Immunofluorescence immunohistochemical staining showed localization of cathepsins B and D to the endothelium of microvessels within the keloid-associated lymphoid tissues and localization of cathepsin G to the tryptase-positive perivascular cells. Western blotting confirmed semiquantitative levels of cathepsins B and D in keloid tissue samples and keloid-derived primary cell lines. Reverse transcription quantitative polymerase chain reaction showed quantitative transcriptional activation of cathepsins B and D in keloid tissue samples and keloid-derived primary cell lines and cathepsin G in keloid tissue samples. Enzyme activity assays demonstrated functional activity of cathepsins B and D.

Conclusion: Cathepsins B, D, and G are expressed by the embryonic stem cell-like population within the keloid-associated lymphoid tissues of keloid lesions and may act to bypass the renin-angiotensin system, suggesting a potential therapeutic target using renin-angiotensin system modulators and cathepsin inhibitors.

PubMed Disclaimer

References

    1. Zhang Q, Yamaza T, Kelly AP, et al. Tumor-like stem cells derived from human keloid are governed by the inflammatory niche driven by IL-17/IL-6 axis. PLoS One 2009;4:e7798.
    1. Grant C, Chudakova DA, Itinteang T, et al. Expression of embryonic stem cell markers in keloid-associated lymphoid tissue. J Clin Pathol. 2016;69:643–646.
    1. Ogawa R. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci. 2017;18:e606.
    1. English RS, Shenefelt PD. Keloids and hypertrophic scars. Dermatol Surg. 1999;25:631–638.
    1. Bakry OA, Samaka RM, Basha MA, Tharwat A, El Meadawy I. Hematopoietic stem cells: Do they have a role in keloid pathogenesis? Ultrastruct Pathol. 2014;38:55–65.

LinkOut - more resources