Silencing of topical proline hydroxylase domain 2 promotes the healing of rat diabetic wounds by phosphorylating AMPK.

Autor: Xie D; Southwest Medical University, No. 1 Section 1, Xianglin Road, Luzhou City, Sichuan Province, 646000, China.; National Key Clinical Construction Specialty, Wound Repair & Regeneration Laboratory, Department of Plastic & Burn Surgery, Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou,Sichuan Province, 646000, China., Liu M; Southwest Medical University, No. 1 Section 1, Xianglin Road, Luzhou City, Sichuan Province, 646000, China.; National Key Clinical Construction Specialty, Wound Repair & Regeneration Laboratory, Department of Plastic & Burn Surgery, Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou,Sichuan Province, 646000, China., Lin Y; Southwest Medical University, No. 1 Section 1, Xianglin Road, Luzhou City, Sichuan Province, 646000, China.; National Key Clinical Construction Specialty, Wound Repair & Regeneration Laboratory, Department of Plastic & Burn Surgery, Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou,Sichuan Province, 646000, China., Liu X; Southwest Medical University, No. 1 Section 1, Xianglin Road, Luzhou City, Sichuan Province, 646000, China.; National Key Clinical Construction Specialty, Wound Repair & Regeneration Laboratory, Department of Plastic & Burn Surgery, Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou,Sichuan Province, 646000, China., Yan H; Southwest Medical University, No. 1 Section 1, Xianglin Road, Luzhou City, Sichuan Province, 646000, China.; National Key Clinical Construction Specialty, Wound Repair & Regeneration Laboratory, Department of Plastic & Burn Surgery, Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou,Sichuan Province, 646000, China.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Dec 01; Vol. 18 (12), pp. e0294566. Date of Electronic Publication: 2023 Dec 01 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0294566
Abstrakt: Background: For diabetic ulcers, the impaired response to hypoxia is a key feature associated with delayed healing. In the early phase of hypoxia, hypoxic signaling activates the AMPK system through direct phosphorylation of the PHD2 pathway, producing a significant endogenous hypoxic protective effect.
Methods: Twenty Sprague-Dawley (SD) rats were randomly divided into two groups: treatment (sh-PHD2) and control (sh-Control). Using lentiviral encapsulation of PHD2-shRNA and transfection, the silencing efficiency of PHD2 expression was verified in rat dermal fibroblasts (RDF) and in rat aortic endothelial cells (RAECs). Changes in the ability of RDF and RAECs to proliferate, migrate, and in the rate of ATP production were observed and then tested after inhibition of AMPK phosphorylation using dorsomorphin. The lentiviral preparation was injected directly into the wounds of rats and wound healing was recorded periodically to calculate the healing rate. Wounded tissues were excised after 14 days and the efficiency of PHD2 silencing, as well as the expression of growth factors, was examined using molecular biology methods. Histological examination was performed to assess CD31 expression and therefore determine effects on angiogenesis.
Results: Lentiviral-encapsulated PHD2-sh-RNA effectively suppressed PHD2 expression and improved the proliferation, migration, and ATP production rate of RDF and RAEC, which were restored to their previous levels after inhibition of AMPK. The rate of wound healing, vascular growth, and expression of growth factors were significantly improved in diabetic-model rats after local silencing of PHD2 expression.
Conclusion: Silencing of PHD2 promoted wound healing in diabetic-model SD rats by activating AMPK phosphorylation.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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