Inhibition of prostaglandin transporter (PGT) promotes perfusion and vascularization and accelerates wound healing in non-diabetic and diabetic rats

Zhongbo Liu, Outhiriaradjou Benard, Mahrukh M. Syeda, Victor L. Schuster, Yuling Chi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Peripheral ischemia, resulting from diminished arterial flow and defective local vascularization, is one of the main causes of impaired wound healing in diabetes. Vasodilatory prostaglandins (PGs), including PGE2 and PGI2, regulate blood flow in peripheral tissues. PGs also stimulate angiogenesis by inducing vascular endothelial growth factor. However, PG levels are reduced in diabetes mainly due to enhanced degradation. We hypothesized that inhibition of the prostaglandin transporter (PGT) (SLCO2A1), which mediates the degradation of PGs, would increase blood flow and stimulate vascularization, thereby mitigating peripheral ischemia and accelerating wound healing in diabetes. Here we report that inhibiting PGT with intravenously injected PGT inhibitor, T26A, increased blood flow in ischemic hind limbs created in non-diabetic rats and streptozotocin induced diabetic rats. Systemic, or combined with topical, T26A accelerated closure of cutaneous wounds. Immunohistochemical examination revealed that inhibition of PGT enhanced vascularization (marked by larger numbers of vessels formed by CD34+ cells), and accelerated re-epithelialization of cutaneous wounds. In cultured primary human bone marrow CD34+ cells and human epidermal keratinocytes (HEKs) either inhibiting or silencing PGT increased migration in both cell lines. Thus PGT directly regulates mobilization of endothelial progenitor cells (EPCs) and HEKs, which could contribute to PGT-mediated vascularization and re-epithelialization. At the molecular level, systemic inhibition of PGT raised circulating PGE2. Taken together, our data demonstrate that PGT modulates arterial blood flow, mobilization of EPCs and HEKs, and vascularization and epithelialization in wound healing by regulating vasodilatory and pro-angiogenic PGs.

Original languageEnglish (US)
Article number133615
JournalPLoS One
Volume10
Issue number7
DOIs
StatePublished - Jul 31 2015

Fingerprint

tissue repair
Wound Healing
prostaglandins
Prostaglandins
transporters
Rats
Perfusion
rats
blood flow
keratinocytes
Blood
Keratinocytes
Medical problems
Re-Epithelialization
diabetes
Endothelial cells
Dinoprostone
ischemia
animal injuries
endothelial cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Inhibition of prostaglandin transporter (PGT) promotes perfusion and vascularization and accelerates wound healing in non-diabetic and diabetic rats. / Liu, Zhongbo; Benard, Outhiriaradjou; Syeda, Mahrukh M.; Schuster, Victor L.; Chi, Yuling.

In: PLoS One, Vol. 10, No. 7, 133615, 31.07.2015.

Research output: Contribution to journalArticle

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