Role of chymase in the local renin-angiotensin system in keloids: inhibition of chymase may be an effective therapeutic approach to treat keloids

Drug Des Devel Ther. 2015 Aug 28:9:4979-88. doi: 10.2147/DDDT.S87842. eCollection 2015.

Abstract

Background: Histologically, keloids contain excess fibroblasts and an overabundance of dermal collagen. Recently, it was reported that chymase induced a profibrotic response via transforming growth factor-β1 (TGF-β1)/Smad activation in keloid fibroblasts (KFs). However, the role of chymase in the local renin-angiotensin system (RAS) in keloids has not been elucidated. This study aims to determine whether chymase plays an important role in the local RAS in keloids.

Methods: We compared the expression and activity of chymase in keloids and normal skin tissues using Western blotting and radioimmunoassay, and studied the expression of TGF-β1, interleukin-1β, collagen I, hydroxyproline, and angiotensin II in KFs after chymase and inhibitors' treatment.

Results: The results revealed an increased activity of chymase in keloid tissues, and that chymase enhanced the expression of angiotensin II, collagen I, TGF-β1, and interleukin-1β in KFs. Blockade of the chymase pathway involved in the local RAS lowered the expression of these signaling factors.

Conclusion: This research suggests that inhibition of chymase might be an effective therapeutic approach to improve the clinical treatment of keloids.

Keywords: angiotensin II; chymase; pathological scar; therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Angiotensin II / metabolism
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Case-Control Studies
  • Cells, Cultured
  • Chymases / antagonists & inhibitors
  • Chymases / metabolism*
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Hydroxyproline / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Keloid / drug therapy
  • Keloid / enzymology*
  • Keloid / genetics
  • Keloid / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Renin-Angiotensin System* / drug effects
  • Serine Proteinase Inhibitors / pharmacology
  • Signal Transduction / drug effects
  • Skin / drug effects
  • Skin / enzymology*
  • Skin / pathology
  • Time Factors
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Young Adult

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Collagen Type I
  • IL1B protein, human
  • Interleukin-1beta
  • RNA, Messenger
  • Serine Proteinase Inhibitors
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Angiotensin II
  • Chymases
  • Hydroxyproline