Hydrophilic bile acid, ursodeoxycholic acid attenuates the effect of tgf-beta 1 on human tenon's fibroblast

• Main Authors: Roslan, Zulaika, Hanafi, Noorul Izzati, Kadir, Siti Hamimah Sheikh Abdul, Noh, Siti Munirah Md, Abd Talib, Fatin Nur Asyiqin, Subrayan, Visvaraja, Vasudevan, Sushil, Latip, Normala Abdul
• Format: Article
• Published: Penerbit UTM Press, Universiti Teknologi Malaysia 2021
• Subjects: RE Ophthalmology
• Online Access: http://eprints.um.edu.my/34929/

Introduction: Trabeculectomy is performed to lower IOP in glaucoma. Excessive scarring of the filtering bleb was reported post-surgery and thus lead to failed trabeculectomy. The excessive scarring occurs due to elevated level of TGF-beta 1 and thus leading to differentiation of tenon's fibroblast to myofibroblast. Ursodeoxycholic acid (UDCA), the most hydrophilic bile acid, reported as beneficial agent for the treatment of ocular diseases. This study aimed to investigate whether UDCA is able to reduce the differentiation of fibroblast to myofibroblast in TGF-beta 1-induced human tenons fibroblast (HTF). Material and Methods: Primary HTFs were obtained and divided into untreated group, TGF-beta 1 treated group (20 ng/ml), UDCA treated group (100 mu M) and TGF-beta 1 co-treated with UDCA (combination) group. All cells were subjected for immunostaining (alpha-SMA and F-actin expression), PCR array (downstream target of TGF-beta 1: Nf-kappa beta, JUN, TIMP1, SMAD3, SMAD2) and western blot (F-actin expression). The statistically significance was set to p < 0.05 and 4 biological replicates were used. Results: The expression of alpha-SMA and F-actin suggest that UDCA inhibits the fibrous structure of striated actin induces by TGF-beta 1 as this actin were highly expressed in TGF-beta only group. No significance changes in downstream target genes of TGF-beta 1 except for Nf-kappa beta 1. Interestingly, protein expression of ERK 1/2 and gene expression of Nf-kappa beta 1 were significantly decreased in combination group (TGF-beta 1 with UDCA) compared to TGF-beta 1 only group. Conclusion: UDCA attenuates the effect of TGF-beta 1 on human Tenon's fibroblast by downregulating the expression of alpha-SMA and F-actin expression which could be mediated by ERK1/2 and NF-kappa beta 1.