Substance P enhances cellular migration and inhibits senescence in human dermal fibroblasts under hyperglycemic conditions

Biochem Biophys Res Commun. 2020 Feb 19;522(4):917-923. doi: 10.1016/j.bbrc.2019.11.172. Epub 2019 Dec 2.

Abstract

Diabetes induces cellular dysfunction in dermal fibroblasts, such as impairment in migration, which is a major cause of chronic wound. Here, we demonstrated that the migration of human dermal fibroblasts was impaired under a high glucose culture condition. Substance P (SP) rescued the impaired migration of the fibroblasts. The activity of Rac1, Rho-associated kinase (ROCK), and Src was required for SP-mediated rescue of fibroblast migration. SP activated Rac1 and Src, whereas, NSC23766, a Rac1 inhibitor, and PP1 and PP2, Src inhibitors, inhibited SP-mediated enhancement of fibroblast migration. Y-27632, a ROCK inhibitor, inhibited the SP-mediated rescue of fibroblast migration. Senescence-associated β-galactosidase activity increased in human dermal fibroblasts cultured in a high glucose environment, but SP inhibited the β-galactosidase activity of the fibroblasts. These results suggest that SP promotes the migration of human dermal fibroblasts in diabetic-condition-mimicking cultures via the activity of Rac1, ROCK, and Src, and inhibits fibroblast senescence in hyperglycemic cultures.

Keywords: Fibroblast; Migration; Senescence; Substance P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / drug effects*
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dermis / pathology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Glucose / toxicity
  • Humans
  • Hyperglycemia / pathology*
  • Substance P / pharmacology*
  • rac1 GTP-Binding Protein / metabolism
  • rho-Associated Kinases / metabolism
  • src-Family Kinases / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Substance P
  • src-Family Kinases
  • rho-Associated Kinases
  • rac1 GTP-Binding Protein
  • Glucose