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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

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Rosuvastatin attenuates tubulointerstitial fibrosis by targeting the HOXA13 USAG1 BMP7 pathway

Donghwan Oh1, Hyo Jeong Kim2, Seok-Hyung Kim3

  • 1Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea.

Scientific Reports
|April 20, 2026
PubMed

Insights

Rosuvastatin reduces kidney fibrosis by activating bone morphogenetic protein-7 (BMP-7) signaling. This statin therapy upregulates homeobox protein Hox-A13 (HOXA13) and downregulates uterine sensitization-associated gene-1 (USAG-1) to combat fibrosis.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Statins are recognized for antifibrotic properties, yet their precise mechanisms remain elusive.
  • Kidney fibrosis is a significant contributor to chronic kidney disease progression.
  • Understanding the molecular pathways involved in kidney fibrosis is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the antifibrotic effects of rosuvastatin in a preclinical model of chronic kidney fibrosis.
  • To elucidate the underlying molecular mechanisms of rosuvastatin's antifibrotic action in kidney cells.

Main Methods:

  • Utilized a unilateral ischemic reperfusion injury and contralateral nephrectomy (uIRIx) mouse model to induce chronic kidney fibrosis.
  • Administered rosuvastatin orally to mice and analyzed kidney fibrosis markers and signaling pathways.
  • Employed transforming growth factor-β1 (TGF-β1)-stimulated Madin-Darby canine kidney (MDCK) cells, including HOXA13 knockdown, to study cellular responses to rosuvastatin.

Main Results:

  • Rosuvastatin treatment attenuated tubulointerstitial fibrosis in uIRIx mice, reducing markers like α-smooth muscle actin (α-SMA) and collagen I.
  • In vitro, rosuvastatin reversed TGF-β1-induced increases in fibrotic markers (α-SMA, fibronectin, collagen 1) in MDCK cells.
  • The drug modulated Smad3 and Smad1/5/9 phosphorylation, indicating involvement of bone morphogenetic protein-7 (BMP-7) signaling.
  • Rosuvastatin decreased uterine sensitization-associated gene-1 (USAG-1) expression, potentially via increased homeobox protein Hox-A13 (HOXA13) expression.

Conclusions:

  • Rosuvastatin demonstrates significant antifibrotic effects in both in vivo and in vitro models of kidney fibrosis.
  • The mechanism involves the activation of BMP-7 signaling.
  • Upregulation of HOXA13 and downregulation of USAG-1 are key pathways through which rosuvastatin exerts its antifibrotic action.
Keywords:
BMP-7FibrosisHOXA13StatinsUSAG-1

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