Decreased MCP-1/CCR2 axis-mediated chemotactic effect of conjunctival fibroblasts after transdifferentiation into

Utako Tsutsumi-Kuroda1, Toshihiro Inoue1, Akiko Futakuchi1

  • 1Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Japan.

Experimental Eye Research
|February 20, 2018
PubMed

Insights

Human conjunctival fibroblasts (HConFs) lose chemotactic effects on monocytes after transforming into myofibroblasts. This change is linked to reduced monocyte chemoattractant protein-1 (MCP-1) via the MCP-1/CCR2 pathway.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Immunology

Background:

  • Human conjunctival fibroblasts (HConFs) play a role in ocular tissue homeostasis.
  • Fibroblast transdifferentiation into myofibroblasts is implicated in fibrotic diseases.

Purpose of the Study:

  • To investigate the alteration in HConF chemotactic properties following transdifferentiation into myofibroblasts.
  • To elucidate the molecular mechanisms underlying these changes, focusing on monocyte chemoattractant protein-1 (MCP-1).

Main Methods:

  • HConFs were induced to transdifferentiate into myofibroblasts using transforming growth factor-beta2 (TGF-β2).
  • Cytokine levels in conditioned media were quantified using multiplex immunoassays.
  • Chemotactic activity was assessed using Boyden chamber assays with THP-1 monocyte cells.

Main Results:

  • Transdifferentiation significantly decreased MCP-1 concentration in HConF conditioned media (P < 0.001).
  • The chemotactic effect of HConFs on THP-1 cells was reduced post-transdifferentiation (P = 0.032).
  • Neutralization of MCP-1 and antagonism of C-C chemokine receptor type 2 (CCR2) inhibited monocyte migration.

Conclusions:

  • Transdifferentiation of HConFs into myofibroblasts diminishes their chemotactic influence on monocytes.
  • The MCP-1/CCR2 signaling pathway is a key mediator of this reduced chemotaxis.
  • These findings offer insights into the cellular mechanisms in ocular fibrotic conditions.

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