Razzaqy, - and Reni Prastyani, - and Yulia Primitasari, - and Maftuchah Rochmanti, - (2019) Down regulation of the expression of MMP-3 and TIMP-1 by Metformin regardless of TNF-α level in an in vitro lens capsule fibrosis model. Biochemical and Cellular Archives, 19 (Supp.2). 4791-4y795. ISSN 0972-5075

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Abstract

ABSTRACT : Metformin, of biguanide groups, was found to possess some anti-inflammatory and anti-fibrotic ability. The drug also showed the capability of inhibiting human lens epithelial cells (HLECs) migration in vitro. Therefore, the aim of this study was to investigate the potential of metformin in reducing the expression of TNF-α as the key cytokine of inflammatory process as well as MMP-3 and TIMP-1 in the early proliferative phase of epithelial-mesenchymal transition (EMT) in lens capsule fibrosis. This study uses HLECs, as initiator of EMT in the development of posterior capsular fibrosis after surgery. These were isolated from the anterior capsule ofacataractous eye. The HLECs were cultured and divided into 4 groups, i.e., FBS 10% control group, as well as the metformin 0.1 mM, 0.5 mM and 1.0 mM treatment groups. The expression of TNF-α was assessed 6 hours after intervention using ELISA, while MMP-3 and TIMP-1 immunofluorescence were evaluated 7 days following metformin administration. The data were analyzed using through One-way ANOVA followed by post hoc test at 95% confidence interval (p<0.05). Low concentration of TNF-á was detected in all groups, with the lowest in FBS 10% group (5.9896±0.0357 pg/mL). Similarly, metformin decreases the expression of MMP-3 and TIMP-1 with mean intensity of 1.8069 × 105 ±1.2715 × 105 pixels and 2.6662 × 105 ± 1.6261 × 105 pixels, which were respectively found to be significantly lower than control group (p<0.05). This result showed metformin role in early proliferative phase of lens EMT directly without TNF-α attenuation. Metformin has an anti-fibrotic role by downregulating proteolytic enzyme such as MMP-3 and TIMP-1 regardless the expression of TNF-α.

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