Inhibition of class I HDACs attenuates renal interstitial fibrosis in a murine model
Related Experiment Video
Updated: Jan 28, 2026
Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
Published on: April 25, 2025
Min Yang1, Gen Chen2, Xue Zhang3
1Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
Abstract:
Renal interstitial fibrosis is the most common of all the forms of chronic kidney disease (CKD). Research has shown that histone deacetylases (HDACs) participate in the process leading to renal fibrosis. However, the effects of class I HDAC inhibitors on the mechanisms of onset and progression of renal interstitial fibrosis are still unclear. Here, we present the effects and mechanisms of action of FK228 (a selective inhibitor of class I HDACs) in the murine model of unilateral ureteral obstruction (UUO) and in vitro models. We investigated the antifibrotic role of FK228 in a murine model of UUO. We used two key effector cell populations, rat renal interstitial fibroblasts and renal tubular epithelial cells exposed to recombinant transforming growth factor-beta 1 (TGF-β1), to explore the mechanistic pathways among in vitro models. The results indicated that FK228 significantly suppressed the production of extracellular matrix (ECM) in both in vivo and in vitro models. FK228 inhibited renal fibroblast activation and proliferation and increased the acetylation of histone H3. We found that FK228 also inhibited the small mothers against decapentaplegic (Smad) and non-Smad signaling pathways. So FK228 could significantly suppress renal interstitial fibrosis via Smad and non-Smad pathways. FK228 may be the basis for a new and effective medicine for alleviating renal fibrosis in the future.
Insights
FK228, a class I histone deacetylase inhibitor, effectively suppresses renal interstitial fibrosis by reducing extracellular matrix production and inhibiting key signaling pathways. This offers potential for new treatments for chronic kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Renal interstitial fibrosis is a common cause of chronic kidney disease (CKD).
- Histone deacetylases (HDACs) are implicated in renal fibrosis development.
- The specific role of class I HDAC inhibitors in renal fibrosis remains unclear.
Purpose of the Study:
- To investigate the antifibrotic effects and mechanisms of FK228, a selective class I HDAC inhibitor.
- To explore FK228's impact on renal interstitial fibroblasts and tubular epithelial cells.
Main Methods:
- Utilized a murine model of unilateral ureteral obstruction (UUO).
- Employed in vitro models with rat renal interstitial fibroblasts and tubular epithelial cells treated with transforming growth factor-beta 1 (TGF-β1).
- Assessed extracellular matrix (ECM) production, fibroblast activation/proliferation, histone H3 acetylation, and Smad/non-Smad signaling pathways.
Main Results:
- FK228 significantly reduced ECM production in both in vivo and in vitro models.
- FK228 inhibited renal fibroblast activation and proliferation.
- FK228 increased histone H3 acetylation and suppressed Smad and non-Smad signaling pathways.
Conclusions:
- FK228 demonstrates significant antifibrotic effects in renal interstitial fibrosis.
- The mechanism involves inhibition of Smad and non-Smad pathways and increased histone acetylation.
- FK228 shows promise as a potential therapeutic agent for renal fibrosis.
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