Lysophosphatidic Acid Modulates TGF-ß2-Induced Biological Phenotype in Human Conjunctival Fibroblasts.
Life (Basel)
; 14(6)2024 Jun 17.
Article
em En
| MEDLINE
| ID: mdl-38929752
ABSTRACT
BACKGROUND:
Although lysophosphatidic acid (LPA) is known to have multiple pathophysiological roles, its contributions to ocular tissues, especially conjunctival fibrogenesis, remain to be elucidated.METHODS:
To study this issue, the effects of LPA on transforming growth factor-ß2 (TGF-ß2)-induced fibrogenesis of two-dimensional (2D) and three-dimensional (3D) cultures of human conjunctival fibroblasts (HconF) were examined by the following analyses (1) planar proliferation determined by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran permeability measurements, (2) real-time metabolic analyses, (3) measurements of the size and stiffness of 3D spheroids, and (4) mRNA expression of extracellular matrix (ECM) molecules and their modulators.RESULTS:
LPA had no effect on TGF-ß2-induced increase in the planar proliferation of HconF cells. LPA induced a more quiescent metabolic state in 2D HconF cells, but this metabolic suppression by LPA was partially blunted in the presence of TGF-ß2. In contrast, LPA caused a substantial decrease in the hardness of 3D HconF spheroids independently of TGF-ß2. In agreement with these different LPA-induced effects between 2D and 3D cultured HconF cells, mRNA expressions of ECM and their modulators were differently modulated.CONCLUSION:
The findings that LPA induced the inhibition of both TGF-ß2-related and -unrelated subepithelial proliferation of HconF cells may be clinically applicable.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article