pp 1–10 | Cite as

Matrix metalloproteinase 9 induces keratinocyte apoptosis through FasL/Fas pathway in diabetic wound

  • Ying Liang
  • Chuan Yang
  • Yongqing Lin
  • Yasir Parviz
  • Kan Sun
  • Wei Wang
  • Meng RenEmail author
  • Li YanEmail author


Apoptosis is a mechanism to remove unwanted cells in the tissue. In diabetic wound, which is characterized by delayed healing process, excessive apoptosis is documented and plays a crucial role. Matrix metalloproteinase 9 (MMP9), which is elevated in non-healed diabetic wound, is necessary for healing process but its abnormality resulted in a delayed healing. The classical function of MMP9 is the degradation of extracellular matrix (ECM). However, there is some literature evidence that MMP9 triggers cell apoptosis. Whether the excessive MMP9 contributes to epidermis cell apoptosis in delayed healing diabetic wound and the underlying mechanisms is not clear. In this study, we aimed to explore whether MMP9 induced keratinocyte apoptosis and investigate the plausible mechanisms. Our in vitro study showed that advanced glycation end products (AGEs) induced keratinocyte apoptosis and enhanced MMP9 level. Besides, MMP9, both intra-cellular expressions and extra-cellular supplement, promoted cell apoptosis. Further, MMP9 resulted in an increased expression of FasL, other than Fas and p53. These findings identified a novel effect that MMP9 exerted in delayed diabetic wound healing, owing to a pro-apoptotic effect on keratinocyte, which was mediated by an increase of FasL expression. This study increases understanding of elevated MMP9 which is involved in diabetic wound repair and offers some insights into novel future therapies.


Advanced glycation end products Matrix metalloproteinase 9 Apoptosis Signaling pathway 



This study was funded by the National Natural Science Foundation of China (81770827, 81471034).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

10495_2019_1536_MOESM1_ESM.tif (19.4 mb)
Supplemental figure (not mentioned in the article, just to identify keratinocyte). a. Human keratinocytes culture (200×). b. Keratin secretion observed by microscope. (A). Keratin images in normal microscope (100×). (B). Keratin images in immunofluorescence microscopy (100×). (C). Cell nucleus images in immunofluorescence microscopy (100×). (TIF 19888 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology, Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina
  2. 2.Department of Cardiology, Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina
  3. 3.Division of Cardiology, Center for Interventional Vascular Therapy, New York-Presbyterian HospitalColumbia UniversityNew YorkUSA

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