Heat shock transcription factor 1 affects kidney tubular cell migration by regulating the TGF‑β1‑Smad2/3 signaling pathway

Mol Med Rep. 2019 Nov;20(5):4323-4330. doi: 10.3892/mmr.2019.10689. Epub 2019 Sep 16.

Abstract

Cell migration is important for renal recovery from tubular cell injury. Heat shock transcription factor 1 (HSF1) is a well‑studied regulatory factor that is active during acute kidney injury. HSF1 is also involved in the migration process during tumor metastasis. Therefore, we hypothesized that HSF1 may promote the recovery of renal function by affecting kidney tubular cell migration. A wound healing assay was used to examine the cell migration rate. The results demonstrated that the migration of rat kidney proximal tubular cells (RPTCs) was increased following knockdown of HSF1. In addition, the invasion ability of HSF1 knockdown RPTCs was also significantly upregulated. The present study also identified that transforming growth factor‑β1 (TGF‑β1) was highly expressed at the edge of the wound in control cells, and its expression was further increased upon knockdown of HSF1. Inhibition of TGF‑β1 signaling prevented RPTC HSF1 knockdown cell migration, suggesting that HSF1‑regulated RPTC cell migration was dependent on the TGF‑β1 signaling pathway. Furthermore, phosphorylation of TGF‑β1 and Smad2/3 was induced in HSF1 knockdown cells. Together, these results suggest that HSF1 may suppress RPTC migration by inhibiting the activation of the TGF‑β1‑Smad2/3 signaling pathway.

MeSH terms

  • Cell Movement / genetics
  • Epithelial Cells / metabolism*
  • Gene Knockdown Techniques
  • Heat Shock Transcription Factors / genetics
  • Heat Shock Transcription Factors / metabolism*
  • Kidney Tubules / metabolism*
  • Signal Transduction*
  • Smad2 Protein / metabolism*
  • Smad3 Protein / metabolism*
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Heat Shock Transcription Factors
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta1