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Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers.
Br J Dermatol. 2004 Dec; 151(6):1189-96.BJ

Abstract

BACKGROUND

The plasminogen activation system represents a potent mechanism of extracellular proteolysis and is an essential component of normal wound healing. It has also been implicated in the pathogenesis of chronic, nonhealing ulcers. Traditionally, urokinase-type plasminogen activator (uPA) has been associated with pericellular proteolytic activity involved in tissue remodelling processes, and tissue-type plasminogen activator (tPA) mainly with intravascular fibrinolysis.

OBJECTIVES

The present study was conducted to characterize the spatial distribution of the various plasminogen activation system components in chronic ulcers and acute, well-granulating wounds.

METHODS

The expression of uPA, tPA, urokinase receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and vitronectin was investigated by immunohistochemical staining, in addition to uPA, tPA and PAI-1 expression by in-situ hybridization, in samples from eight chronic venous ulcers, five decubitus ulcers, five well-granulating acute wounds and five normal skin samples.

RESULTS

In chronic venous leg ulcers tPA mRNA was detected in basal and suprabasal keratinocytes at the leading wound edge, while in well-granulating wounds and in decubitus ulcers tPA mRNA was expressed only in a few keratinocytes. However, tPA was widely expressed in fibroblast- and macrophage-like cells in the stroma of well-granulating wounds, while less tPA was detected in the granulation tissue of chronic ulcers. tPA mRNA and protein were localized in the superficial granular layers in normal skin. Although no qualitative differences in expression of uPA, PAI-1 or uPAR in the wound edge keratinocytes in chronic ulcers vs. normally granulating wounds were found, their expressions were more pronounced in the granulation tissue of well-granulating wounds.

CONCLUSIONS

These results suggest that in poorly healing venous leg ulcers, the pattern of tPA expression is altered in keratinocytes at the leading edge of the wound, and the patterns of tPA, uPA and PAI-1 expression are altered in the granulation tissue.

Authors+Show Affiliations

Department of Virology, Haartman Institute, P.O. 21, FI-00014, University of Helsinki, Finland. miina.weckroth@helsinki.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15606514

Citation

Weckroth, M, et al. "Epithelial Tissue-type Plasminogen Activator Expression, Unlike That of Urokinase, Its Receptor, and Plasminogen Activator Inhibitor-1, Is Increased in Chronic Venous Ulcers." The British Journal of Dermatology, vol. 151, no. 6, 2004, pp. 1189-96.
Weckroth M, Vaheri A, Virolainen S, et al. Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers. Br J Dermatol. 2004;151(6):1189-96.
Weckroth, M., Vaheri, A., Virolainen, S., Saarialho-Kere, U., Jahkola, T., & Sirén, V. (2004). Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers. The British Journal of Dermatology, 151(6), 1189-96.
Weckroth M, et al. Epithelial Tissue-type Plasminogen Activator Expression, Unlike That of Urokinase, Its Receptor, and Plasminogen Activator Inhibitor-1, Is Increased in Chronic Venous Ulcers. Br J Dermatol. 2004;151(6):1189-96. PubMed PMID: 15606514.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers. AU - Weckroth,M, AU - Vaheri,A, AU - Virolainen,S, AU - Saarialho-Kere,U, AU - Jahkola,T, AU - Sirén,V, PY - 2004/12/21/pubmed PY - 2005/4/14/medline PY - 2004/12/21/entrez SP - 1189 EP - 96 JF - The British journal of dermatology JO - Br J Dermatol VL - 151 IS - 6 N2 - BACKGROUND: The plasminogen activation system represents a potent mechanism of extracellular proteolysis and is an essential component of normal wound healing. It has also been implicated in the pathogenesis of chronic, nonhealing ulcers. Traditionally, urokinase-type plasminogen activator (uPA) has been associated with pericellular proteolytic activity involved in tissue remodelling processes, and tissue-type plasminogen activator (tPA) mainly with intravascular fibrinolysis. OBJECTIVES: The present study was conducted to characterize the spatial distribution of the various plasminogen activation system components in chronic ulcers and acute, well-granulating wounds. METHODS: The expression of uPA, tPA, urokinase receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and vitronectin was investigated by immunohistochemical staining, in addition to uPA, tPA and PAI-1 expression by in-situ hybridization, in samples from eight chronic venous ulcers, five decubitus ulcers, five well-granulating acute wounds and five normal skin samples. RESULTS: In chronic venous leg ulcers tPA mRNA was detected in basal and suprabasal keratinocytes at the leading wound edge, while in well-granulating wounds and in decubitus ulcers tPA mRNA was expressed only in a few keratinocytes. However, tPA was widely expressed in fibroblast- and macrophage-like cells in the stroma of well-granulating wounds, while less tPA was detected in the granulation tissue of chronic ulcers. tPA mRNA and protein were localized in the superficial granular layers in normal skin. Although no qualitative differences in expression of uPA, PAI-1 or uPAR in the wound edge keratinocytes in chronic ulcers vs. normally granulating wounds were found, their expressions were more pronounced in the granulation tissue of well-granulating wounds. CONCLUSIONS: These results suggest that in poorly healing venous leg ulcers, the pattern of tPA expression is altered in keratinocytes at the leading edge of the wound, and the patterns of tPA, uPA and PAI-1 expression are altered in the granulation tissue. SN - 0007-0963 UR - https://www.unboundmedicine.com/medline/citation/15606514/Epithelial_tissue_type_plasminogen_activator_expression_unlike_that_of_urokinase_its_receptor_and_plasminogen_activator_inhibitor_1_is_increased_in_chronic_venous_ulcers_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-0963&date=2004&volume=151&issue=6&spage=1189 DB - PRIME DP - Unbound Medicine ER -