miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis

الملخص EN

Sepsis is a severe disease, which results from the excessive inflammatory response to the infection.

Dysfunction of intestinal barrier is a crucial problem in various pathological conditions.

Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis.

Multiple investigations indicate that miR-199a-5p participates in different human diseases.

Nevertheless, little is known on the roles of miR-199a-5p in sepsis.

Herein, we evaluated the mechanism of miR-199a-5p on the intestinal barrier dysfunction in sepsis.

Intestinal mucosa permeability indicators including D-lactic acid, DAO, and FD-40 levels were determined, and they were greatly increased in sepsis.

Then, we proved that miR-199a-5p was induced in sepsis mice tissues and isolated intestinal epithelial cells.

Moreover, miR-199a-5p increased D-lactic acid, DAO, and FD-40 while inhibition of miR-199a-5p exhibited a reversed process.

Additionally, we observed that miR-199a-5p affected the oxidative damage and inflammation in the intestine tissues from sepsis mice.

The content of MDA was elevated whereas SOD was remarkably repressed in the miR-199a-5p mimic group.

IL-6, IL-1β, and TNF-α were induced by miR-199a-5p overexpression while IL-10 was reduced by miR-199a-5p.

Subsequently, surfactant protein D (SP-D) was predicted as the target of miR-199a-5p.

The activation of NF-κB has been identified in sepsis.

Herein, we demonstrated that inhibitor of miR-199a-5p contributed to IEC injury via targeting SP-D and inactivating the NF-κB pathway.

These revealed miR-199a-5p exacerbated the intestinal barrier dysfunction via inhibiting SP-D and activating the NF-κB pathway in sepsis.