Journal article
Continuous NPWT Regulates Fibrosis in Murine Diabetic Wound Healing
PHARMACEUTICS, v 14(10), 2125
Oct 2022
PMID: 36297560
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, -125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP (p = 0.04) but decreased En1 (p = 0.0001) and CD26 (p < 0.0001). The pro-fibrotic factors Vimentin (p = 0.04), alpha-SMA (p = 0.04) and HSP47 (p = 0.0008) were decreased with NPWT. Fibronectin was higher (p = 0.01) and collagen deposition lower in the NPWT group (p = 0.02). NPWT increased cellular proliferation (p = 0.002) and decreased apoptosis (p = 0.03). Western blotting demonstrated increased YAP (p = 0.02) and RhoA (p = 0.03) and decreased Caspase-3 (p = 0.03) with NPWT. NPWT uncouples YAP from EPF activation, through downregulation of Caspace-3, a pro-apoptotic factor linked to keloid formation. Mechanotransduction decreases multiple pro-fibrotic factors. Through this multifactorial process, NPWT significantly decreases fibrosis and offers promising potential as a mode to improve scar appearance.
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Details
- Title
- Continuous NPWT Regulates Fibrosis in Murine Diabetic Wound Healing
- Publication Details
- PHARMACEUTICS, v 14(10), 2125
- Publisher
- MDPI; BASEL
- Grant note
- This work was funded by The Gillian Reny Stepping Strong Center for Trauma Innovation and 3M*KCI (Kinetic Concepts Inc.). S.S. was funded by the UK-US Fulbright commission with an All Disciplines Award. L.F. was funded by the NIH 5 T35 HL11084 fellowship award. M.W. was supported by the Natural Science Foundation from Shenzhen Science and Technology Innovation Commission(20210319172905002) and the Shenzhen Key Medical Discipline Construction Fund (No.SZXK026). Y.R. was supported by the European Research Council Consolidator Grant (ERC-CoG 819933), the LEO Foundation (LF-OC-21-000835) and the European Foundation for the Study of Diabetes (EFSD) Anniversary Fund Programme.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000873812500001
- Scopus ID
- 2-s2.0-85141000493
- Other Identifier
- 991021861196904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy