Microvesicles-delivering Smad7 have advantages over microvesicles in suppressing fibroblast differentiation in a model of Peyronie’s disease

TL;DR

This study shows that microvesicles delivering Smad7 are more effective than regular microvesicles in reducing fibroblast activity in a model of Peyronie’s disease.

Contribution

The study demonstrates that Smad7-loaded microvesicles have superior anti-fibrotic effects compared to standard microvesicles in Peyronie’s disease.

Findings

Smad7-MVs suppressed fibroblast differentiation more effectively than regular MVs in a Peyronie’s disease model.

Both MVs and Smad7-MVs reduced macrophage M1 polarization and fibroblast differentiation in vitro and in vivo.

Smad7-MVs showed a distinct advantage in reducing fibrosis in the tunica albuginea of treated rats.

Abstract

This study compared the differences of microvesicles (MVs) and microvesicles-delivering Smad7 (Smad7-MVs) on macrophage M1 polarization and fibroblast differentiation in a model of Peyronie’s disease (PD).

Overexpression of Smad7 in rat BMSCs was obtained by pCMV5-Smad7 transfection. MVs were collected from rat BMSCs using ultracentrifugation. In cells, 100 µg/mL of MVs or Smad7-MVs were used to treat the 100 ng/mL of lipopolysaccharide (LPS)-induced RAW264.7 cells or 10 ng/mL of recombinant transforming growth factor-β1 (TGF-β1)-induced fibroblasts. The pro-inflammatory cytokines and markers of M1 macrophages were measured in RAW264.7 cells, and the migration and markers of fibroblast differentiation were measured in fibroblasts. In rats, 50 µg of MVs or Smad7-MVs were used to treat the TGF-β1-induced animals. The pathology of tunica albuginea (TA), the markers of M1 macrophages and fibroblast differentiation in the TA were measured.

The MVs or Smad7-MVs treatment suppressed the LPS-induced macrophage M1 polarization and TGF-β1-induced fibroblast differentiation. Moreover, the Smad7-MVs treatment decreased the fibroblast differentiation compared with the MVs treatment. In the TGF-β1-induced TA of rats, MVs or Smad7-MVs treatment ameliorated the TA fibrosis by suppressing the macrophage M1 polarization and fibroblast differentiation. There was no significance on the M1-polarized macrophages between the MVs treatment and the Smad7-MVs treatment. Meanwhile, the Smad7-MVs treatment had an edge in terms of suppressing the fibroblast differentiation in the TGF-β1-induced PD model compared with the MVs treatment.

This study demonstrated that Smad7-MVs treatment had advantages over MVs treatment in suppressing of fibroblast differentiation in a model of PD.

The online version contains supplementary material available at 10.1186/s12896-024-00866-1.

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