Plasminogen is a critical regulator of cutaneous wound healing

Rima Sulniute; Yue Shen; Yong-Zhi Guo; Mahsa Fallah; Nina Ahlskog; Lina Ny; Olena Rakhimova; Jessica Broden; Hege Boija; Aliyeh Moghaddam; Jinan Li; Malgorzata Wilczynska; Tor Ny

doi:10.1160/TH15-08-0653

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 115(05): 1001-1009
DOI: 10.1160/TH15-08-0653

Blood Cells, Inflammation and Infection

Schattauer GmbH

Plasminogen is a critical regulator of cutaneous wound healing

Rima Sulniute

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Yue Shen

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Yong-Zhi Guo

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Mahsa Fallah

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Nina Ahlskog

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Lina Ny

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Olena Rakhimova

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Jessica Broden

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Hege Boija

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Aliyeh Moghaddam

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Jinan Li

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Malgorzata Wilczynska

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

,

Tor Ny

¹Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

› Author Affiliations

Abstract

Summary

Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogendeficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chronic inflammation. Delayed formation of granulation tissue suggests that fibroblast function is impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for subsequent steps, including resolution of inflammation and activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing process that is comparable to that in wild-type mice. Besides of being an activator of the inflammatory phase during wound healing, plasminogen is also required for the subsequent termination of inflammation. Based on these results, we propose that plasminogen may be an important future therapeutic agent for wound treatment.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Plasminogen - wound healing - inflammation

Full Text

References

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