Granzyme B inhibits keratinocyte migration by disrupting epidermal growth factor receptor (EGFR)-mediated signaling
| Autor: | Yulia Merkulova, Mehul Sharma, Hongyan Zhao, Leigh G. Parkinson, Kathryn Westendorf, Sheetal A. Raithatha, Robert Chris Bleackley, Yue Shen, David J. Granville |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Keratinocytes Clinical Biochemistry Biochemistry Granzymes GZMB Cell Line 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Humans Epidermal growth factor receptor Keratinocyte migration Phosphorylation Molecular Biology Wound Healing integumentary system biology Chemistry Cell migration 3. Good health Granzyme B ErbB Receptors HaCaT 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Cancer research biology.protein Signal transduction Keratinocyte Signal Transduction |
| Zdroj: | Biological chemistry. 397(9) |
| ISSN: | 1437-4315 |
| Popis: | Chronic non-healing wounds including diabetic, venous, and decubitus skin ulcers are currently lacking effective therapies. Non-healing diabetic ulcers can lead to amputations as progress into a highly chronic state before detection and existing treatments for these wounds often fail. Granzyme B (GzmB) is a serine protease that was, until recently, believed to function exclusively in cytotoxic lymphocyte-mediated apoptosis. However, during excessive or chronic inflammation, GzmB can accumulate in the extracellular milieu, retain its activity, and cleave a number of important extracellular proteins. Epidermal growth factor receptor (EGFR) is a transmembrane receptor involved in cellular processes such as proliferation and migration. EGFR signaling is integral to the wound healing process. The present study investigated the effects of GzmB on keratinocyte cell migration using HaCaT cell line. Using electric cell-substrate impedance sensing and scratch assays, the present study demonstrates that GzmB inhibits keratinocyte migration by interfering with the EGFR pathway. GzmB limited cell transition into a migratory morphology and was found to reduce ligand-induced EGFR phosphorylation. Inhibition of GzmB reversed the aforementioned effects. In summary, data from the present study suggest key role for GzmB in the pathogenesis of impaired wound healing through the impairment of EGFR signaling and cell migration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|