Emodin Ameliorates Severe Acute Pancreatitis-Associated Acute Lung Injury in Rats by Modulating Exosome-Specific miRNA Expression Profiles

Qi Yang; Yalan Luo; Peng Ge; Bowen Lan; Jin Liu; Haiyun Wen; Yinan Cao; Zhenxuan Sun; Guixin Zhang; Huiming Yuan; Lihua Zhang; Hailong Chen

doi:10.2147/IJN.S428924

Emodin Ameliorates Severe Acute Pancreatitis-Associated Acute Lung Injury in Rats by Modulating Exosome-Specific miRNA Expression Profiles

Int J Nanomedicine. 2023 Nov 15:18:6743-6761. doi: 10.2147/IJN.S428924. eCollection 2023.

Authors

Qi Yang^{1

2

3

4}, Yalan Luo^{1

2

3}, Peng Ge^{1

2

3}, Bowen Lan^{1

2

3}, Jin Liu^{1

2

3}, Haiyun Wen^{1

2

3}, Yinan Cao^{1

2

3}, Zhenxuan Sun^{1

2

3}, Guixin Zhang^{1

2

3}, Huiming Yuan⁵, Lihua Zhang⁵, Hailong Chen^{1

2

3}

Affiliations

¹ Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People's Republic of China.
² Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People's Republic of China.
³ Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People's Republic of China.
⁴ Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, People's Republic of China.
⁵ CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, 116023, People's Republic of China.

Abstract

Background: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear.

Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO.

Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats.

Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO.

Keywords: acute lung injury; emodin; exosome; microRNA; severe acute pancreatitis.

MeSH terms

Acute Disease
Acute Lung Injury* / drug therapy
Animals
Emodin* / pharmacology
Exosomes* / metabolism
MicroRNAs* / genetics
MicroRNAs* / metabolism
Pancreatitis* / chemically induced
Pancreatitis* / drug therapy
Rats

Substances

Emodin
MicroRNAs

Grants and funding

This study was supported by National Natural Science Foundation of China (NO. 82074158 and 82274311), National Key R&D Program of China (NO. 2019YFE0119300), and Applied Basic Research Program of Liaoning Province (NO. 2023JH2/101300126).