Tubastatin A suppresses the proliferation of fibroblasts in epidural fibrosis through phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway

Objectives: This study was designed to explore the effect of tubastatin A (Tub A) on epidural fibrosis and the underlying mechanism.

Methods: Histone deacetylase 6 (HDAC6)-overexpressed fibroblasts were constructed, and the effect of Tub A on the proliferation of activated fibroblasts was detected by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine (EdU) and cell cycle assay. Besides, 20 Sprague-Dawley rats were subjected to animal laminectomy model construction and then randomly treated with 4% dimethyl sulfoxide (DMSO) (diluted in 0.9% saline) or Tub A (10 mg/kg/day), separately. The expression of HDAC6 and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway-related proteins was measured in epidural fibrosis tissues.

Key findings: HDAC6 was overexpressed in activated fibroblasts and epidural scar tissues of rat models. Cell proliferation was remarkably elevated in HDAC6-overexpressed fibroblasts, which was reflected by cell viability, EdU and flow cytometry-based cell cycle assay, and paralleled with the increased expression of phosphorylated PI3K, AKT and mTOR, which was remarkably reversed following Tub A treatment. 740Y-P activator addition significantly reversed the declined fibroblast proliferation induced by Tub A. The expressions of PI3K/AKT/mTOR pathway-related proteins were also reduced in epidural tissues in rat models with Tub A treatment.

Conclusion: Tub A could prevent epidural fibrosis formation by inhibiting fibroblast proliferation through mediating PI3K/AKT/mTOR pathway.

Related Products

Cat.No.	Product Name	Information
S8049	Tubastatin A	Tubastatin A is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotes autophagy and increases apoptosis.

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Apoptosis related Autophagy HDAC