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
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Yue Shen
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Yong-Zhi Guo
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Mahsa Fallah
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Nina Ahlskog
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Lina Ny
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Olena Rakhimova
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Jessica Broden
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Hege Boija
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Aliyeh Moghaddam
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Jinan Li
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Malgorzata Wilczynska
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
,
Tor Ny
1   Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden
› Author Affiliations
Financial Support: This research was supported by the National Cancer Foundation, Diabetesfonden, and The Medical Faculty of Umeå University.
Further Information

Publication History

Received: 17 August 2015

Accepted after major revision: 05 January 2016

Publication Date:
06 December 2017 (online)

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.

 
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