Asiatic Acid Improves Extracellular Matrix Remodeling in Vocal Fold Scarring Via SMAD7 Activation

Vocal fold (VF) fibroblasts are the central target for developing new strategies for the treatment of VF scarring and fibrosis. Asiatic acid (AA) is a triterpenoid derivate with antifibrotic properties. However, the effect of AA in VF scarring is poorly understood. The objective of this study was to investigate the potential application of AA as a therapeutic treatment in VF scarring.

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The functional expression of SMAD7 was knocked down with recombinant adenoviruses and adeno-associated viruses carrying shRNAs in the in vitro and in vivo models, which were constructed to investigate AA's antifibrotic function. The expression of collagens and SMADs in cultured human and rabbit cell lines and animal models was evaluated with quantitative reverse transcription polymerase chain reaction and immunohistochemistry labeling, respectively. Cell migration capacity and contraction in VF fibroblast cell lines were also evaluated.

AA downregulated the downstream fibrotic activation in a dose-dependent manner. Meanwhile, AA attenuated VF scarring/fibrosis by reducing collagen deposition. Furthermore, the antifibrotic effects of AA were associated with the upregulation of SMAD7. In contrast, knockdown of SMAD7 inhibited the effect of AA on transforming growth factor-beta-1 (TGF-β1) stimulation, which suggests a central role for SMAD7 in AA-induced antifibrotic activities during VF fibrosis.

We concluded that AA, which is a novel therapeutic candidate for preventing VF scarring/fibrosis, might exert its antifibrotic effect via the TGF-β1/SMAD signaling pathway.

NA Laryngoscope, 132:1237-1244, 2022.