Abstract: Objective To investigate how miR-181c influences cardiopulmonary recovery afterlung transplantation in mice by targeting mitochondrial calcium uniporter 1 (MICU1) . Methods Fifty-four adult male C57BL / 6 mice were randomly assigned to six groups (n = 9 each): Normalgroup, Lung Transplantation group, Lung Transplantation + inhibitor-NC group, Lung Transplantation + miR-181c-inhibitor group, Lung Transplantation + miR-181c-inhibitor + si-NC group, andLung Transplantation + miR-181c-inhibitor + si-MICU1 group. The Normal group underwent anesthesia and thoracotomy only; the other groups received autologous left lung orthotopic transplantation,followed by weekly tail-vein injections (0. 2 mL) of saline or 10 nmol / mL inhibitor / siRNA for 60days. qRT-PCR and Western blotting were use to detect miR-181c and MICU1 mRNA and protein expression levels. Dual-luciferase gene reporter assay was performed to verify the targeting relationship between miR-181c and MICU1. Pulmonary pathology was assessed by hematoxylin-eosin (HE) staining. Pulmonary function was assessed using a small animal pulmonary function test system [0. 15 s forced expiratory volume as a percentage of forced vital capacity ( FEV0. 15 / FVC), peak expiratory flow (PEF), maximum ventilation volume ( MVV), diffusing capacity of the lung for carbon monoxide ( DLCO), and residual volume ( RV)] . Cardiac function was detected using small animal ultrasound imaging technology [ left ventricular ejection fraction ( LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter ( LVESD), left ventricular end-diastolic volume ( LVEDV), and left ventricular end-systolic volume (LVESV)] . Results The expression level of miR-181c was elevated and that of MICU1 was reduced in the Lung transplantation group versus those in the Normalgroup (P< 0. 05), with a significant negative correlation (r = - 0. 378, P = 4. 21 × 10 - 4 ) . miR- 181c mimic suppressed MICU1-3′ UTR-WT luciferase activity ( P < 0. 05 ) but not 3′ UTRMUT. Inhibition of miR-181c expression restored MICU1 expression, and reduced lung lesions, and improved FEV0. 15 / FVC, PEF, MVV, DLCO, LVEF, LVFS, and decreased RV, LVESD, LVEDV, LVESV ( all P < 0. 05) . These gains were abolished by co-silencing MICU1 and miR-181c (P< 0. 05) . Conclusion miR-181c impairs cardiopulmonary recovery after lung transplantation bytargeting MICU1. miR-181c inhibition enhances post-transplant function.

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