Effect of Kelulut Honey on the Cellular Dynamics of TGFβ-Induced Epithelial to Mesenchymal Transition in Primary Human Keratinocytes.

Abid Nordin,Shiplu Roy Chowdhury,Aminuddin Bin Saim,Ruszymah Bt Hj Idrus

doi:10.3390/ijerph17093229

Abstract

Over-induction of epithelial to mesenchymal transition (EMT) by tumor growth factor beta (TGFβ) in keratinocytes is a key feature in keloid scar. The present work seeks to investigate the effect of Kelulut honey (KH) on TGFβ-induced EMT in human primary keratinocytes. Image analysis of the real time observation of TGFβ-induced keratinocytes revealed a faster wound closure and individual migration velocity compared to the untreated control. TGFβ-induced keratinocytes also have reduced circularity and display a classic EMT protein expression. Treatment of 0.0015% (v/v) KH reverses these effects. In untreated keratinocytes, KH resulted in slower initial wound closure and individual migration velocity, which sped up later on, resulting in greater wound closure at the final time point. KH treatment also led to greater directional migration compared to the control. KH treatment caused reduced circularity in keratinocytes but displayed a partial EMT protein expression. Taken together, the findings suggest the therapeutic potential of KH in preventing keloid scar by attenuating TGFβ-induced EMT.

Highlights

Over-induction of epithelial to mesenchymal transition (EMT) by transforming growth factor beta (TGFβ) in keratinocytes is a key feature in scarred wound and keloid formation [1]
When protein expression of the epithelial marker E-cadherin and mesenchymal marker vimentin was evaluated, TGFβ induction resulted in the classical EMT indicator of E-cadherin downregulation and vimentin upregulation
Our results suggest the validity of the quantitative morphological parameters to be used as indicator of EMT activation in human primary keratinocytes

Summary

Introduction

Over-induction of epithelial to mesenchymal transition (EMT) by transforming growth factor beta (TGFβ) in keratinocytes is a key feature in scarred wound and keloid formation [1]. Keloid is the formation of excessive fibrous tissue during the process of cutaneous wound healing. It can extend beyond the original wound borders, resulting in disfiguring scar [2]. EMT key features are the loss of epithelial integrity and gain of mesenchymal cell motility. The phenotypic transition of the cells is typically marked by the reduction of molecular marker that represents the epithelial state such as E-cadherin, or the elevation of molecular marker that represents the mesenchymal state such as vimentin [5]

Objectives

Methods

Discussion

Conclusion