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Updated: Apr 20, 2026
A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
MSCs with ACE II gene affect apoptosis pathway of acute lung injury induced by bleomycin
Xiaomiao Zhang1, Fengying Gao, Qian Li
11Department of Thoracic Surgery, First People's Hospital Affiliated to Shanghai Jiaotong University , Shanghai , PR China.
Purpose:
The aim of this study was to evaluate the effect and related mechanisms of Mesenchymal stem cells (MSCs) and Angiotensin converting enzyme II (ACE II) on acute lung injury (ALI).
Methods:
MSCs were separated from umbilical cord cells, and the changes of phenotype before and after ACE II silence were observed using Flow Cytometer. ALI model was induced by 10 mg/mL bleomycin in 60 Balb/c mice, and the rest 8 mice were regarded as the baseline group. The mice were randomly divided into four groups (n = 15): control, ACE II, stem, and stem + ACE II. The apoptotic index (AI) was calculated using TUNEL, and the detection of protein and mRNA of Bax, Bak and p53, Bcl-2, Grp78, CHOP and Caspase 12 were used by western-blot and RT-PCR, respectively.
Results:
The umbilical cord cells differentiated into stable MSCs about 14 days, and ACE II transfection reached a peak at the 5th day after transfection. ACE II silence did not affect the phenotype of MSCs. All the proteins and mRNAs expression except Bcl-2 in the stem and stem + ACE II were significantly lower than those in control from 8 h (p < 0.05, p < 0.01), while Bcl-2 exhibited an opposite trend. Stem + ACE II performed a better effect than single stem in most indexes, including AI (p < 0.05, p < 0.01).
Conclusions:
The co-administration of MSCs and ACE II can significantly suppress apoptosis in ALI mice, and may be an effective clinical treatment for ALI.
Insights
Mesenchymal stem cells (MSCs) combined with Angiotensin converting enzyme II (ACE II) significantly reduced apoptosis in acute lung injury (ALI) mice. This combination therapy shows promise as an effective clinical treatment for ALI.
Area of Science:
- Regenerative Medicine
- Molecular Biology
- Pulmonology
Background:
- Acute lung injury (ALI) is a critical condition with limited treatment options.
- Mesenchymal stem cells (MSCs) have shown therapeutic potential in various injury models.
- The role of Angiotensin converting enzyme II (ACE II) in ALI pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the therapeutic effects of MSCs and ACE II on ALI.
- To explore the underlying molecular mechanisms of MSCs and ACE II in ALI.
- To evaluate the combined efficacy of MSCs and ACE II in an ALI mouse model.
Main Methods:
- MSCs were isolated and characterized.
- An ALI mouse model was established using bleomycin.
- Mice were treated with MSCs, ACE II, or a combination therapy.
- Apoptosis and expression of key proteins/mRNAs (Bax, Bak, p53, Bcl-2, Grp78, CHOP, Caspase 12) were assessed.
Main Results:
- MSCs and ACE II co-administration significantly reduced the apoptotic index in ALI mice compared to single treatments.
- Combined therapy demonstrated superior efficacy in suppressing apoptosis-related gene and protein expression.
- ACE II silence did not alter MSC phenotype, indicating MSCs' inherent properties were maintained.
Conclusions:
- Co-administration of MSCs and ACE II effectively suppresses apoptosis in ALI.
- This combination therapy represents a promising and novel clinical strategy for managing ALI.
- Further research into the synergistic mechanisms is warranted for clinical translation.
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