Epalrestat induces cell proliferation and migration in endothelial cells via mTOR activation through PI3/Akt signaling

Kunihiro Suzuki, Seiichi Tanaka, Kazunori Yanagi, Tosie Iijima, Mai Niitani, Ciro Coletta, Csaba Szabo, Yoshimasa Aso

Research output: Contribution to journalArticle

Abstract

Angiogenesis is a major physiological response to ischemia that involves development of new capillaries and collateral circulation from preexisting vessels, and endothelial cell (EC) proliferation and migration are crucial events for this process. Epalrestat, an aldose reductase inhibitor, is used as a therapeutic agent for the treatment of diabetic peripheral neuropathy. We examined the effect of epalrestat on the proliferation and migration of a mouse microvascular endothelial cell line (bEnd3 cells) measured by scratch wound assay and cell proliferation assay. Epalrestat significantly enhanced the proliferation and migration of bEnd3 cells. The addition of epalrestat resulted in the phosphorylation of Akt and p70 S6 kinase (p70S6K), and this effect was attenuated by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR), inhibited p70S6K phosphorylation only. Both rapamycin and LY294002 inhibited epalrestat-induced proliferation and migration. These data suggest that epalrestat may activate PI3/Akt/mTOR signaling and that this pathway contributes to the proliferation and migration of EC.

Original languageEnglish (US)
Pages (from-to)105-111
Number of pages7
JournalDiabetology International
Volume5
Issue number2
DOIs
StatePublished - 2014

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Sirolimus
Cell Movement
Endothelial Cells
Cell Proliferation
70-kDa Ribosomal Protein S6 Kinases
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Phosphorylation
Phosphatidylinositol 3-Kinase
Aldehyde Reductase
Collateral Circulation
Diabetic Neuropathies
Peripheral Nervous System Diseases
epalrestat
Ischemia
Cell Line
Wounds and Injuries

Keywords

  • Akt
  • Endothelial Cell
  • Epalrestat
  • Mammalian target of rapamycin (mTOR)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Epalrestat induces cell proliferation and migration in endothelial cells via mTOR activation through PI3/Akt signaling. / Suzuki, Kunihiro; Tanaka, Seiichi; Yanagi, Kazunori; Iijima, Tosie; Niitani, Mai; Coletta, Ciro; Szabo, Csaba; Aso, Yoshimasa.

In: Diabetology International, Vol. 5, No. 2, 2014, p. 105-111.

Research output: Contribution to journalArticle

Suzuki, Kunihiro ; Tanaka, Seiichi ; Yanagi, Kazunori ; Iijima, Tosie ; Niitani, Mai ; Coletta, Ciro ; Szabo, Csaba ; Aso, Yoshimasa. / Epalrestat induces cell proliferation and migration in endothelial cells via mTOR activation through PI3/Akt signaling. In: Diabetology International. 2014 ; Vol. 5, No. 2. pp. 105-111.
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