Related Experiment Video
Updated: May 7, 2026
Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
[Expression of PEPT2 mRNA in lung tissue of rats with pulmonary fibrosis]
Li Li1, Dianhua Wang, Xuan Zhang
1Department of Bio-immunical Therapy, the Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.
Background And Objective:
Pulmonary fibrosis is a common pathological phenomenon in lung cancer patients after chemotherapy or radiotherapy. It is also a key hindrance to the transport of drugs to lung tissue. Peptide transporters have become a target of the rational design of peptides and peptide drugs. The aim of this study is to investigates the expression of peptide transporter 2 (PEPT2) mRNA in the lungs of rats with bleomycin (BLM)-induced pulmonary fibrosis.
Methods:
Fifty healthy adult Sprague-Dawley rats were randomly divided into five groups. One group was untreated (control), the second group was injected with normal saline solution (NS), and the three remaining groups were treated with a single dose of bleomycin to induce pulmonary fibrosis (BLM). Rats from the NS group were killed by exsanguination on day 14. Rats from the BLM group were killed by exsanguination on days 7, 14, and 28. The lung samples were observed under light microscopy and the hydroxyproline concentration was determined. The expression levels of PEPT2 mRNA were measured by RT-PCR.
Results:
The morphological study showed that collagenous fiber proliferated in the lungs of rats injected with BLM, indicating pulmonary fibrosis. This proliferation was apparent at 14 d post-injection and especially at 28 d post-injection. Hydroxyproline levels increased seven days post-injection compared with the control group and NS group, but there was no significant statistical difference (P>0.05). Hydroxyproline levels significantly increased (P<0.05) 14 d and 28 d post-infection. The change in the lung tissue pathology coincided with the change in hydroxyproline levels. There were no significant changes of pulmonary PEPT2 mRNA expression levels among the different groups (P>0.05).
Conclusion:
PEPT2 is a potential peptide drug target in the treatment of pulmonary fibrosis, although there were no significant changes of PEPT2 mRNA expression in the lungs of rats with bleomycin-induced pulmonary fibrosis.
Insights
Pulmonary fibrosis, a complication of lung cancer treatment, hinders drug delivery. This study found no significant change in peptide transporter 2 (PEPT2) mRNA expression in fibrotic rat lungs, suggesting PEPT2 may not be a direct therapeutic target for this condition.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Molecular Biology
Context:
- Pulmonary fibrosis is a significant challenge in lung cancer patients undergoing chemotherapy or radiotherapy, impeding effective drug transport to lung tissues.
- Peptide transporters are increasingly recognized as crucial targets for the development of novel peptide-based therapeutics.
- Understanding the role of specific transporters like peptide transporter 2 (PEPT2) in fibrotic lung disease is essential for targeted drug design.
Purpose:
- To investigate the expression levels of peptide transporter 2 (PEPT2) mRNA in the lungs of rats with bleomycin (BLM)-induced pulmonary fibrosis.
- To assess the correlation between pulmonary fibrosis development and PEPT2 mRNA expression.
- To evaluate the potential of PEPT2 as a therapeutic target for pulmonary fibrosis.
Summary:
- Bleomycin administration successfully induced pulmonary fibrosis in Sprague-Dawley rats, characterized by increased collagen deposition and hydroxyproline levels, particularly at 14 and 28 days post-injection.
- Despite the development of significant pulmonary fibrosis, quantitative analysis using RT-PCR revealed no statistically significant alterations in PEPT2 mRNA expression levels in the lung tissues across different experimental groups.
- Morphological and biochemical markers of fibrosis correlated with the time course of bleomycin treatment, but PEPT2 mRNA expression remained stable.
Impact:
- The findings suggest that while PEPT2 is a relevant transporter for peptide drugs, its mRNA expression in lung tissue does not significantly change during bleomycin-induced pulmonary fibrosis.
- This indicates that PEPT2 may not be a direct therapeutic target for modulating established pulmonary fibrosis in this model.
- Further research is warranted to explore other mechanisms or transporters involved in drug delivery to fibrotic lung tissue.
