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Journal of Endocrinological Investigation

, Volume 42, Issue 11, pp 1307–1317 | Cite as

Expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer and its effect on angiogenesis of diabetic foot ulcer rats

  • C.-J. LinEmail author
  • Y.-M. Lan
  • M.-Q. Ou
  • L.-Q. Ji
  • S.-D. Lin
Original Article

Abstract

Objective

To investigate the expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer (DFU) and its effect on angiogenesis in DFU rats.

Methods

The serum levels of miR-217, HIF-1α and VEGF were detected in DFU and simple diabetes mellitus (DM) patients, and healthy controls. DFU rat models were established and treated with miR-217 inhibitors and/or HIF-1α siRNA. The ulcer healing of DFU rats was observed. Besides, ELISA method was performed to detect the serum level of HIF-1α, VEGF and inflammatory factors, immunohistochemical (IHC) method to test the micro-vessel density (MVD), as well as qRT-PCR and Western blot to determine expressions of miR-217, HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 in tissues.

Results

The serum levels of miR-217 were up-regulated while HIF-1α and VEGF were down-regulated in DFU patients and rats when compared with DM and healthy controls (all P < 0.05). Dual-luciferase reporter gene assay confirmed that HIF- was the direct target gene of miR-217. DFU rats treated with miR-217 inhibitors had decreased foot ulcer area and accelerated ulcer healing, with significantly reduced inflammatory factors (IL-1β, TNF-α and IL-6), as well as elevated HIF-1α and VEGF (all P < 0.05); meanwhile, they remarkably increased the MVD in foot dorsum wound tissues and the protein expressions of HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 (all P < 0.05).

Conclusion

Inhibiting miR-217 could up-regulate HIF-1α/VEGF pathway to promote angiogenesis and ameliorate inflammation of DFU rats, thereby effectively advancing the healing of ulcerated area.

Keywords

miR-217 HIF-1α VEGF Diabetic foot Angiogenesis 

Notes

Compliance with ethical standards

Conflict of interest

None.

Ethical approval

The clinical research in this study was approved by the Ethics Committee of The First Affiliated Hospital of Shantou University Medical College and conformed to the guidelines of Helsinki Declaration.

Informed consent

All samples were collected after obtaining the informed consent form signed by all the subjects.

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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  • C.-J. Lin
    • 1
    Email author
  • Y.-M. Lan
    • 1
  • M.-Q. Ou
    • 1
  • L.-Q. Ji
    • 1
  • S.-D. Lin
    • 1
  1. 1.Department of Endocrinology and MetabolismThe First Affiliated Hospital of Shantou University Medical CollegeShantouPeople’s Republic of China

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