What question did this study set out to answer?

This research investigates how 7-Ketolithocholic acid (7-KLCA) protects against renal fibrosis and its underlying mechanisms involving FXR.

January 10, 2026Pharmaceuticals0 citationsOpen Access

7-Ketolithocholic Acid Exerts Anti-Renal Fibrotic Effects Through FXR-Mediated Inhibition of TGF-β/Smad and Wnt/β-Catenin Pathways

Q: What does this research mean for the field?

7-Ketolithocholic acid significantly reduces serum creatinine and blood urea nitrogen levels while inhibiting TGF-β/Smad and Wnt/β-catenin pathways in renal fibrosis models. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

QGQicheng GuoHainan University LPLianye PengHainan University JZJingyi ZhangShihezi University

Key Result

7-Ketolithocholic acid significantly reduced serum creatinine and blood urea nitrogen levels while inhibiting TGF-β/Smad and Wnt/β-catenin pathways in renal fibrosis models.

Key Points

This research investigates how 7-Ketolithocholic acid (7-KLCA) protects against renal fibrosis and its underlying mechanisms involving FXR.
In vitro analysis on HK-2/NRK-49F cells using CCK-8, Western blot, and qPCR for fibrosis assessment.
In vivo experiments with mouse models (UUO and adenine-induced) treated with varying doses of 7-KLCA or losartan.
Evaluation of renal injury via H&E/Masson staining and measurement of serum creatinine and blood urea nitrogen levels.
Verification of 7-KLCA-FXR interaction through molecular docking, CETSA, and DARTS.
Measurement of FXR downstream genes and proteins using Western blot and qPCR.
7-KLCA decreased fibrotic protein levels like fibronectin and collagen-I.
It reduced LPS-induced inflammatory factors including IL-1β and IL-6.
In mice, 7-KLCA reduced renal swelling, collagen accumulation, and tubular damage.
Treatment lowered serum creatinine and blood urea nitrogen levels, indicating improved kidney function.
7-KLCA bound to FXR, enhancing its stability and function, and inhibited the TGF-β/Smad and Wnt/β-catenin pathways.

Structured PICO

Does 7-Ketolithocholic acid reduce renal fibrosis in preclinical models?

Population

In vitro HK-2/NRK-49F cells and in vivo unilateral ureteral obstruction (UUO) and adenine (Ade)-induced mouse models of renal fibrosis

Intervention

7-Ketolithocholic acid (7-KLCA) (low/high-dose)

Comparator

Losartan or untreated controls

Outcome

Renal fibrosis and inflammation (fibrotic proteins, inflammatory factors, renal swelling, collagen deposition, tubular damage, SCR, BUN)surrogate

7-KLCA exerts anti-renal fibrotic effects by targeting FXR and suppressing the TGF-β/Smad and Wnt/β-catenin pathways in preclinical models.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Background/Objectives: To explore the protective effects of 7-Ketolithocholic acid (7-KLCA) against renal fibrosis and its mechanism, focusing on its interaction with farnesoid X receptor (FXR). Methods: In vitro, TGF-β-induced fibrosis in HK-2/NRK-49F cells and LPS-induced inflammation in HK-2 cells were detected by CCK-8, Western blot, and qPCR. In vivo, unilateral ureteral obstruction (UUO) and adenine (Ade)-induced mouse models were treated with a low/high-dose 7-KLCA or losartan. Renal injury was evaluated via H&E/Masson staining, serum creatinine (SCR), and blood urea nitrogen (BUN) levels. The 7-KLCA-FXR interaction was verified by molecular docking, CETSA, and DARTS. FXR downstream genes and related proteins were measured by WB and qPCR. Results: 7-KLCA inhibited the expression of fibrotic proteins (fibronectin, collagen-I) and reduced the LPS-induced release of inflammatory factors (IL-1β, IL-6). In mice, it alleviated renal swelling, collagen deposition, and tubular damage, while lowering serum SCR and BUN levels. Mechanistically, 7-KLCA stably bound to the FXR ligand-binding domain, enhanced its thermal stability and degradation resistance. It upregulated FXR and its downstream genes SHP and FGF15, thereby inhibiting the activation of TGF-β/Smad and Wnt/β-catenin pathways. Conclusions: This is the first study to clarify the molecular mechanism through which 7-KLCA targets FXR and dually suppresses the key pro-fibrotic pathways TGF-β/Smad and Wnt/β-catenin, thereby exerting anti-renal fibrosis effects.

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