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Molecules 2018, 23(9), 2236; https://doi.org/10.3390/molecules23092236

Pomolic Acid Ameliorates Fibroblast Activation and Renal Interstitial Fibrosis through Inhibition of SMAD-STAT Signaling Pathways

1
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Korea
2
Department of Paediatrics, College of Medicine, Yeungnam University, Daegu 42415, Korea
3
College of Pharmacy, Keimyung University, Daegu 42601, Korea
Theses authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 10 August 2018 / Revised: 30 August 2018 / Accepted: 1 September 2018 / Published: 3 September 2018
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Abstract

Fibrosis is a common pathological feature in most kinds of chronic kidney disease. Transforming growth factor β1 (TGF-β1) signaling is the master pathway regulating kidney fibrosis pathogenesis, in which mothers against decapentaplegic homolog 3 (SMAD3) with signal transducer and activator of transcription 3 (STAT3) act as the integrator of various pro-fibrosis signals. We examine the effects of pomolic acid (PA) on mice with unilateral ureteral obstruction (UUO) and TGF-β1 stimulated kidney fibroblast cells. UUO mice were observed severe tubular atrophy, and tubulointerstitial fibrosis and extracellular matrix (ECM) deposition at seven days postoperatively. However, PA-treated UUO mice demonstrated only moderate injury, minimal fibrosis, and larger reductions in the expression of ECM protein and epithelial-mesenchymal transition (EMT) progress. PA inhibited the SMAD-STAT phosphorylation in UUO mice. PA effects were also confirmed in TGF-β1 stimulated kidney fibroblast cells. In this study, we first demonstrated that PA ameliorates fibroblast activation and renal interstitial fibrosis. Our results indicate that PA may be useful as a potential candidate in the prevention of chronic kidney disease. View Full-Text
Keywords: TGF-β1; Pomolic acid; Renal fibrosis; fibroblast; ECM TGF-β1; Pomolic acid; Renal fibrosis; fibroblast; ECM
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Park, J.-H.; Jang, K.M.; An, H.J.; Kim, J.-Y.; Gwon, M.-G.; Gu, H.; Park, B.; Park, K.-K. Pomolic Acid Ameliorates Fibroblast Activation and Renal Interstitial Fibrosis through Inhibition of SMAD-STAT Signaling Pathways. Molecules 2018, 23, 2236.

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