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Volume 42 Issue 4
Apr.  2026
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Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(4): 900-907

Effect of Klotho-derived peptide 7 on pancreatic fibrosis in a mouse model of chronic pancreatitis and its mechanism

DOI: 10.12449/JCH260419
  • 1.

    Department of Gastroenterology，Qingyuan Hospital Affiliated to Guangzhou Medical University，Qingyuan，Guangdong 511518，China

  • 2.

    Basic Medical College of Dali University，Dali，Yunnan 671000，China

  • 3.

    Department of Pharmacy，West China Hospital，Sichuan University，Chengdu 610041，China

  • 4.

    School of Pharmacy，Zunyi Medical University，Zunyi，Guizhou 563000，China

Research funding:

Guangdong Provincial Medical Science and Technology Research Fund (A2022163);

Guangdong Provincial Medical Science and Technology Research Fund (A2024690);

Guangdong Provincial Administration of Traditional Chinese Medicine Scientific Research Project (20231412);

Guangdong Provincial Administration of Traditional Chinese Medicine Scientific Research Project (20251478);

Wu Jieping Medical Foundation Special Research Fund (320.6750.2024-03-49);

Guangdong Basic and Applied Basic Research Fund (2025A1515010072)

More Information
  • Corresponding author: QI Ling， qiling1718@gzhmu.edu.cn （ORCID： 0000-0002-6275-3599）; LI Fengjin，wklifengjin@163.com （ORCID： 0000-0002-8405-7922）
  • Received Date: 2025-10-09
  • Accepted Date: 2025-11-25
  • Published Date: 2026-04-25
    Abstract
  •   Objective  To investigate the anti‑pancreatic fibrosis mechanism of Klotho‑derived peptide 7 （KL7） by observing its effect on a mouse model of chronic pancreatitis （CP） induced by cerulean， and to provide a basis for clinical medication.  Methods  A total of 40 male BALB/c mice were randomly divided into control group， model group， low-dose KL7 group （2 mg/kg）， and high-dose KL7 group （4 mg/kg）， with 10 mice in each group. All mice except those in the control group were given intraperitoneal injection of cerulean （50 μg/kg） 6 times a day at an interval of 1 hour， twice a week for 4 consecutive weeks to establish a model of CP. The mice in the low-dose KL7 group and the high-dose KL7 group were treated with different doses of KL7 once a day for 4 consecutive weeks. In vivo imaging was used to observe the accumulation of KL7 in the pancreas； molecular docking was used to detect the binding of KL7 to transforming growth factor-β type Ⅱ receptor （TβRⅡ）； the mice were measured in terms of body weight and pancreatic weight； HE staining was used to observe the pathological changes of pancreatic tissue； Masson staining was used to observe the degree of pancreatic fibrosis； immunohistochemical staining was used to measure the expression of α-smooth muscle actin （α-SMA） and type Ⅰ collagen （COL1A1）； Western blotting was used to measure the protein expression levels of α-SMA， TβRII， and phosphorylated small mothers against decapentaplegic homolog 2/3 （p-Smad2/3） in pancreatic tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test and the Dunnett’s-T3 test were used for further comparison between two groups.  Results  KL7 was significantly enriched in the pancreatic tissue of CP mice， and there was a strong binding activity between KL7 and TβRⅡ. Compared with the control group， the model group had significant reductions in pancreatic mass and relative pancreatic mass （P<0.000 1）， with disordered structure of pancreatic tissue， an increase in inflammatory cell infiltration， and significant increases in fibrosis degree， the positive areas of α-SMA and COL1A1 （P<0.000 1）， and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.05）. Compared with the model group， the high-dose KL7 group had significant increases in pancreatic mass and relative pancreatic mass （P<0.01）， with alleviation of structural damage of pancreatic tissue and inflammatory cell infiltration， a significant reduction in fibrosis degree， and significant reductions in the positive areas of α-SMA and COL1A1 （P<0.001） and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.01）.  Conclusion  KL7 has a significant targeted therapeutic effect on pancreatic fibrosis in CP mice through specific binding of KL7 to TβRⅡ， thereby inhibiting the activation of the TGF-β/Smad signaling pathway.

     

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