Possible effects of miR29a downregulation on keloid scar formation


Koçak Sezgin A. , Demirdöver C., Akdoğan G.

45th FEBS Congress, “Molecules of Life: Towards New Horizons“,, Ljubljana, Slovenia, 3 - 08 July 2021, pp.146

  • Publication Type: Conference Paper / Summary Text
  • Doi Number: 10.1002/2211-5463.13205
  • City: Ljubljana
  • Country: Slovenia
  • Page Numbers: pp.146

Abstract

Abnormal wound healing can cause keloid scar formation. Keloids are fibrous benign tumours that continue growing beyond the wound boundaries. It is characterized

by increased collagen accumulation. Therefore, targeting collagen synthesis may be the right approach for treatment. Evidence is emerging regarding the efficacy of the

miR29 family in fibrotic diseases and extracellular matrix proteins are dominant among target molecules. In this study, we examined the role of miR29 family in keloids,

HSP47 and LOX for collagen maturation and collagen synthesis through the TGFb/

Smad pathway. We determined the skin keloid and control tissue miR29 family

gene levels via qPCR. After determining miR29 expressions in keloid scar tissues, we inhibited miR29a in primary keloid fibroblasts. We checked the protein levels

related to collagen synthesis by using western blotting. TGFb/

Smad pathway gene levels were determined by using qPCR. Extracellular LOX activity was measured

with a fluorescent kit, and TIMP1

protein levels were assessed with ELISA. As a result, it has been found a significant increase in fibronectin, COL1A and LOXL2

protein levels, and LOX activity. These parameters proved that miR29a affects the collagen synthesis process and increases collagen synthesis. On the other hand, the

downregulation of miR29a in keloids increased TGFb/

Smad pathway activity. TIMP1

gene levels upregulated with this activity, but this was not reflected in the

extracellular TIMP1

protein level. This may indicate that miR29a affects TGFb,

TGFb

stimulates TIMP1,

but this stimulation may not be reflected in the protein

level of TIMP1

and may be a cause of the irregularity in keloid histopathology. These findings indicate that miR29a is effective in keloid formation and this activity is

related to the expression level of miR29a.