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. 2021 Sep 9;19(1):386.
doi: 10.1186/s12967-021-03022-x.

microRNA-193-3p attenuates myocardial injury of mice with sepsis via STAT3/HMGB1 axis

Jianyuan Pan  1   2 , Buse Alexan  2 , Dorn Dennis  2   3 , Chiristine Bettina  2   3 , Laeuf Ilona Mariya Christoph  3 , Yongqin Tang  4   5
Affiliations

microRNA-193-3p attenuates myocardial injury of mice with sepsis via STAT3/HMGB1 axis

Jianyuan Pan et al. J Transl Med. .

Retraction in

Abstract

Objective: Little is known regarding the functional role of microRNA-193-3p (miR-193-3p) in sepsis. Hence, the aim of the present study was to investigate the effect of miR-193-3p on myocardial injury in mice with sepsis and its mechanism through the regulation of signal transducers and activators of transcription 3 (STAT3).

Methods: The mice model of sepsis was established by cecal ligation and puncture (CLP), septic mice were injected with miR-193-3p agomir, miR-193-3p antagomir or siRNA-STAT3. The expression of miR-193-3p, STAT3 and HMGB1 in the myocardial tissue of septic mice were detected. Cardiac ultrasound, hemodynamics, myocardial injury markers, inflammatory factors and cardiomyocyte apoptosis in septic mice were measured.

Results: MiR-193-3p expression was reduced while STAT3 expression was increased in septic mice. Down-regulated STAT3 or up-regulated miR-193-3p improved cardiac function, attenuated myocardial injury, inflammation and cardiomyocyte apoptosis in septic mice. Knockdown STAT3 reversed the role of inhibited miR-193-3p for mice with sepsis. miR-193-3p targeted STAT3, thereby inhibiting HMGB1 expression.

Conclusion: This study provides evidence that miR-193-3p targets STAT3 expression to reduce HMGB1 expression, thereby reducing septic myocardial damage. MiR-193-3p might be a potential candidate marker and therapeutic target for sepsis.

Keywords: Cecal ligation and puncture; High-mobility group box 1 protein; Inflammatory reaction; MicroRNA-193-3p; Sepsis; Signal transducers and activators of transcription 3.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Myocardial injury of mice with sepsis. A–C Echocardiographic parameters comparison of mice; D–F Hemodynamic indexes of mice; G–I ELISA detected cTnI, BNP and HMGB1 in the serum; J–L ELISA detected LDH, CK and CK-MB expression levels; M–O ELISA detected TNF-α, IL-6 and IL-1β levels; n = 15; *P < 0.05 vs. the sham group
Fig. 2
Fig. 2
miR-193-3p is degraded in mice with sepsis. A HE staining detected myocardial tissue pathology (×400); B Masson staining detected myocardial tissue fibrosis (×400); C TUNEL staining detected myocardial tissue apoptosis (×400); D ELISA detected MPO activity; E RT-qPCR detected miR-193-3p expression; n = 15; *P < 0.05 vs. the sham group
Fig. 3
Fig. 3
Restored miR-193-3p inhibits myocardial injury in mice with sepsis. A RT-qPCR detected miR-193-3p expression; B–D Echocardiographic parameters comparison of mice; E–G hemodynamic indexes of mice; H–J ELISA detected cTnI, BNP and HMGB1 in the serum; K–M ELISA detected LDH, CK and CK-MB expression levels; N–P ELISA detected TNF-α, IL-6 and IL-1β levels; n = 15; *P < 0.05 vs. the CLP + miRagomir NC group
Fig. 4
Fig. 4
Restored miR-193-3p inhibits myocardial injury in mice with sepsis. A HE staining detected myocardial tissue pathology (×400); B Masson staining detected myocardial tissue fibrosis (×400); C TUNEL staining detected myocardial tissue apoptosis (×400); D ELISA detected MPO activity; n = 15; *P < 0.05 vs. the CLP + miRagomir NC group
Fig. 5
Fig. 5
STAT3 is the target gene of miR-193-3p. A Western blot detected STAT3 protein expression; B online software to predict the binding site of miR-193-3p to STAT3; C the targeting relationship between miR-193-3p and STAT3 was verified by luciferase activity test (N = 3); D RT-qPCR detected STAT3 expression; E Western blot detected STAT3 protein expression; F Co-IP detected the binding relationship between HMGB1 and STAT3 (N = 3); G, H RT-qPCR and Western blot detected the expression level of HMGB1; n = 15
Fig. 6
Fig. 6
Loss of STAT3 attenuates myocardial injury in mice with sepsis and reverses the effect of miR-193-3p inhibition on septic mice. A Western blot detected STAT3 protein expression. B–G Echocardiographic parameters and hemodynamic indexes of mice; H–J ELISA detected cTnI, BNP and HMGB1 in the serum; K–M ELISA detected LDH, CK and CK-MB expression levels; N–P ELISA detected TNF-α, IL-6 and IL-1β levels; n = 15; *P < 0.05 vs. the CLP + siRNA-NC group; #P < 0.05 vs. the CLP + miR-193-3p antagomir + siRNA-NC group
Fig. 7
Fig. 7
Loss of STAT3 attenuates myocardial injury in mice with sepsis and reverses the effect of miR-193-3p inhibition on septic mice. A HE staining detected myocardial tissue pathology (×400); B Masson staining detected myocardial tissue fibrosis (×400); C TUNEL staining detected myocardial tissue apoptosis (×400); D ELISA detected MPO activity; n = 15; *P < 0.05 vs. the CLP + siRNA-NC group; #P < 0.05 vs. the CLP + miR-193-3p antagomir + siRNA-NC group
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