2. Academic Validation
  3. Pomolic Acid Ameliorates Fibroblast Activation and Renal Interstitial Fibrosis through Inhibition of SMAD-STAT Signaling Pathways

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

  • Molecules. 2018 Sep 3;23(9):2236. doi: 10.3390/molecules23092236.
Ji-Hyun Park 1,  Kyung Mi Jang 2,  Hyun Jin An 3,  Jung-Yeon Kim 4,  Mi-Gyeong Gwon 5,  Hyemin Gu 6,  Byoungduck Park 7,  Kwan-Kyu Park 8
Affiliations

Affiliations

  • 1 Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Korea. jihyunp@cu.ac.kr.
  • 2 Department of Paediatrics, College of Medicine, Yeungnam University, Daegu 42415, Korea. fortune001j@gmail.com.
  • 3 Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Korea. ahj119@cu.ac.kr.
  • 4 Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Korea. jy1118@cu.ac.kr.
  • 5 Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Korea. daldy88@cu.ac.kr.
  • 6 Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Korea. guhm1207@cu.ac.kr.
  • 7 College of Pharmacy, Keimyung University, Daegu 42601, Korea. bpark@kmu.ac.kr.
  • 8 Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Korea. kkpark@cu.ac.kr.
PMID: 30177595 DOI: 10.3390/molecules23092236
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.

Keywords

ECM; Pomolic acid; Renal fibrosis; TGF-β1; fibroblast.

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