Inhibition of miR-497-3p Downregulates the Expression of Procalcitonin and Ameliorates Bacterial Pneumonia in Mice.

Abstract

Pneumonia is usually caused by a wide variety of pathogen infection. The underlying mechanism contributing to pneumonia remains elusive. Here, the role of microRNA-497-3p (miR-497-3p) was explored in bacterial pneumonia. The expression levels of miR-497-3p and procalcitonin (PCT) in patient serum were detected by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The interaction between miR-497-3p and PCT was further verified in A549 cell line. To further explore the role of miR-497-3p in pneumonia, mouse model of bacterial pneumonia was established via Sp TIGR4 strain (SpT4) infection. Subsequently, LV-miR-497-3p sponge was administrated in mice with bacterial pneumonia. The severity of pneumonia and inflammatory response were evaluated. Serum miR-497-3p and PCT levels increased in patients with bacterial pneumonia and miR-497-3p level positively corrected with the PCT level. The functional assay demonstrated that CALCA is the target of miR-497-3p in the A549 cell line. In mice with bacterial pneumonia, both miR-497-3p and PCT levels were upregulated after SpT4 infection. LV-miR-497-3p sponge administration attenuated pneumonia, accompanied with increasing gain of bodyweight and blood oxygen levels, as well as uninjured lungs. miR-497-3p inhibition attenuates the expression of C-reactive protein (CRP) and inflammatory cytokines in lung tissues of SpT4-infected mice, including nterleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In conclusion, inhibition of miR-497-3p downregulates the expression of procalcitonin and ameliorates bacterial pneumonia in mice.

• Authors: Wenlong Wang, Yitang Zhu, Linlin Yin, Yaoyao Deng, Guoxian Chu, Supin Liu
• Journal: Inflammation (Inflammation) Vol. 43 Issue 6 Pg. 2119-2127 (Dec 2020) ISSN: 1573-2576 [Electronic] United States
• PMID: 32591941 (Publication Type: Journal Article)

Chemical References

• Calca protein, mouse
• Cytokines
• MIRN497 microRNA, human
• MicroRNAs
• Procalcitonin
• Tumor Necrosis Factor-alpha
• mirn497 microRNA, mouse
• Calcitonin Gene-Related Peptide

Topics

• A549 Cells
• Animals
• Calcitonin Gene-Related Peptide
• Cytokines (metabolism)
• Down-Regulation
• Gene Expression Profiling
• Humans
• Inflammation
• Mice
• Mice, Inbred C57BL
• MicroRNAs (antagonists & inhibitors)
• Pneumonia, Bacterial (metabolism, therapy)
• Procalcitonin (biosynthesis)
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation