Resveratrol Activated Sonic Hedgehog Signaling to Enhance Viability of NIH3T3 Cells in Vitro via Regulation of Sirt1

• Published in: Cellular physiology and biochemistry Vol. 50; no. 4; pp. 1346 - 1360
• Main Authors: Guo, Shuang, Liao, Hongyan, Liu, Jie, Liu, Jing, Tang, Fanren, He, Zhongxiang, Li, Yangchun, Yang, Qin
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Aging; Animals; Apoptosis; Benzamides - pharmacology; Cell Survival - drug effects; Fibroblasts; Gene expression; Hedgehog Proteins - metabolism; Kidneys; Kinases; Mice; Naphthols - pharmacology; NIH 3T3 Cells; NIH3T3 cells; Original Paper; Patched-1 Receptor - metabolism; Primary cilia; Proteins; Resveratrol; Scars; Signal Transduction - drug effects; Sirt1; Sirtinol; Sirtuin 1 - antagonists & inhibitors; Sirtuin 1 - chemistry; Sirtuin 1 - metabolism; Smoothened Receptor - antagonists & inhibitors; Smoothened Receptor - metabolism; Sonic hedgehog signaling; Spinal cord; SRT1720; Stem cells; Stilbenes - pharmacology; Transcription factors; Transcription, Genetic - drug effects; Traumatic brain injury; Up-Regulation - drug effects; Veratrum Alkaloids - pharmacology; Zinc Finger Protein GLI1 - genetics; Zinc Finger Protein GLI1 - metabolism; United States > US; SRT1720; Primary cilia; Sirtinol; Resveratrol; NIH3T3 cells; Sonic hedgehog signaling; Sirt1
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000494593

Background/Aims: Injuries of the brain and spinal cord result in the formation of glial (reactive gliosis) and fibrotic (formed by fibroblasts) scars. Recent studies have shown that the fibrotic scar was much more important for hindering regeneration after brain or spinal cord injury than the astrocytic scar. However, it has been given much less attention for effects and mechanism of fibroblasts during formation of the fibrotic scar. Resveratrol may be a potential anti-scarring agent in burn-related scarring and keloid fibroblasts. However, it is unclear whether and how resveratrol affects formation of the fibrotic scar after brain or spinal cord injury. Earlier studies have shown that the activated Shh signaling has anti-apoptosis, anti-oxidation, anti-inflammation properties. Moreover, resveratrol can activate the Shh signaling. However, it is unclear how resveratrol activates the Shh signaling. Resveratrol is a activator of Sirt1. It is unknown whether resveratrol activates the Shh signaling via Sirt1. Methods: NIH3T3 cells, a fibroblast cell line, were used as model cells and treated with drugs. Cell viability was assessed by Cell Counting Kit 8. The expressions and activity of Shh signaling pathway proteins were evaluated by immunocytochemistry and Western blotting. Transcriptional activity of Gli-1 was detected with Dual-Luciferase Reporter Gene Assay Kit. Results: Resveratrol, Sirt1 agonist STR1720 and recombinant mouse Shh protein, an activator of hedgehog signaling, enhanced the viability of NIH3T3 cells, promoted Smo to translocated to the primary cilia and Gli-1 entered into the nuclei from cytoplasm, and upregulated expressions of Shh, Ptc-1, Smo, and Gli-1 proteins, which can be reversed by Smo antagonist cyclopamine and Sirt1 antagonist Sirtinol. Additionally, resveratrol increased transcriptional activity of Gli-1. Conclusion: We indicate in the first time that it may be mediated by Sirt1 for resveratrol activating the Shh signaling to enhance viability of NIH3T3 cells, and Sirt1 may be a regulator for upstream of the Shh signaling pathway.This study provides a basis for further investigating effects and mechanism of resveratrol during the formation of fibrous scar after brain or spinal cord injury.