All trans retinoic acid modulates peripheral nerve fibroblasts viabilityand apoptosis

Niapour, Nazila and Niapour, Ali and Sheikhkanloui Milanb,, Hamid and Amani, Mohammad and Salehic, Hossein and Najafzadeh, Nowrouz and Gholami, Mohammad Reza (2015) All trans retinoic acid modulates peripheral nerve fibroblasts viabilityand apoptosis. Tissue and Cell, 47. pp. 61-65.

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Abstract

tObjective: Following peripheral nerve injury, residing fibroblasts start to proliferate and accumulate atthe injury site and may participate in neuroma tissue evolution. Retinoic acid has been shown to regulatemany cellular processes and to display anti-proliferative and anti-fibrotic properties. The aim of thisstudy was to investigate the impact of all trans retinoic acid (ATRA) on rat peripheral nerve fibroblasts.Materials and methods: Peripheral nerve fibroblasts and C166 cells were treated with increasing dosesof ATRA (0.05 nM to 1 �M). The viability of cells was determined with 3-(4,5-dimethlthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the number of peripheral nerve fibroblastswas counted after two days of ATRA treatment and alternatively up to the end of next week. Acridineorange/ethidium bromide double staining was implemented to morphologically visualize the possiblemechanism of cell death. For apoptosis, caspase 3/7 activity was measured using Caspase-Glo 3/7 assaykit.Results: MTT assay revealed that 0.05–1 nM of ATRA reduces fibroblasts viabilities. Then, almost a plateaustate was observed from 1 nM to 1 �M of ATRA exposure. Additionally, a deceleration in peripheralnerve fibroblasts growth was confirmed via cell counting. Quantification of acridine orange/ethidiumbromide staining displayed highly increased number of early apoptotic cells following ATRA adminis-tration. Amplified activation of caspase 3/7 was in favor of apoptosis in ATRA treated peripheral nervefibroblasts.Conclusion: The data from the present study demonstrate that ATRA could interfere in peripheral nervefibroblasts viabilities and induce apoptosis. Although more investigations are needed to be implemented,our in vitro results indicate that retinoic acid can probably help the regeneration of injured axon viareducing of fibroblasts growth

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