Absence of miR-223-3p ameliorates hypoxia-induced injury through repressing cardiomyocyte apoptosis and oxidative stress by targeting KLF15.

Apoptosis of cardiomyocytes and oxidant stress are considered essential processes in the progression of cardiovascular diseases. A hypoxic stress which causes apoptosis of cardiomyocytes is the main problem in ischemic heart disease. The aim of the present study was to explore the functional role and potential mechanisms of miR-223-3p in hypoxia-induced cardiomyocyte apoptosis and oxidative stress. Here, we observed a increment of miR-223-3p level accompanied by the decrease of Krüppel-like zinc-finger transcription factor 15 (KLF15) expression in response to hypoxia. Additionally, absence of miR-223-3p manifestly dampened hypoxia-induced cardiomyocyte injury in H9c2 cells, including improving cell viability, attenuating the LDH leakage and preventing cardiomyocyte apoptosis accompanied by an increase in the expression of Bcl-2 and a decrease in the expression of Bax and C-caspase 3 in the setting of hypoxia. Moreover, depletion of miR-223-3p evidently retarded oxidant stress by inhibiting reactive oxygen species generation and lipid peroxidation, as well as enhancing antioxidant enzyme activity in H9c2 cells following exposure to hypoxia. More importantly, KLF15 was a direct and functional target of miR-223-3p. Further data validated that miR-223-3p negatively regulated the expression of KLF15. Mechanistically, deletion of KLF15 partly abrogated the suppressive effects of miR-223-3p deletion on hypoxia-induced cardiomyocyte apoptosis and oxidative stress. Taken all data together, our findings established that our study defines a novel mechanism by which miR-223-3p protects against cardiomyocyte apoptosis and oxidative stress by targeting KLF15, suggesting that the miR-223-3p/KLF15 may be a potential therapeutic target for ischemic heart conditions.

[Expression and significance of interleukin-6, interferon-inducible protein-10 and interleukin-17 in serum and synovial fluid of patients with juvenile idiopathic arthritis].

OBJECTIVE: To detect the disparity of three cytokines interleukin-6 (IL-6), interferon-inducible protein 10 (IP-10) and interleukin-17 (IL-17) in peripheral blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA). METHOD: Serum concentrations of the three cytokines were measured in 27 patients with 13 systemic-onset JIA (sJIA), 14 polyarticular JIA (pJIA) and 28 healthy controls using enzyme-linked immunosorbent assay (ELISA). Nineteen patients with no marked arthritis symptom or only temporary arthralgia were enrolled in probable sJIA group. SF from 18 patients with 7 sJIA, 11 pJIA were examined for cytokine levels. RESULT: (1) The statistically significant difference in serum IL-6 was detected between sJIA and healthy control group [28.0(4.2-59.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P < 0.05], but no significant difference between probable sJIA and healthy control group [11.8(7.7-39.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P > 0.05] was found. There were statistically significant differences between sJIA group and healthy control group in serum concentrations of IL-17 [14.0(9.8-34.3) ng/L vs. 9.8 (7.9-16.2) ng/L, P < 0.05], yet compared to healthy control group, no significant difference in concentration level of IL-17 was found in pJIA Group [14.2(9.9-16.9) ng/L vs. 9.8(7.9-16.2) ng/L, P > 0.05].(2) In sJIA and pJIA SF, the median IP-10 level was significantly higher compared to respective PB levels [619.7 (160.9, 873.1) ng/L vs. 64.8 (27.4-111.9) ng/L;660.9 (401.9, 1349.8) ng/L vs. 97.4 (41.9-222.1) ng/L, P < 0.01, respectively], but there was only significant difference in IL-17 between pJIA SF and PB [22.9 (17.1, 45.8) ng/L vs. 14.2 (9.9-16.9) ng/L, P < 0.01]. CONCLUSION: IL-6 may play more important role in the pathogenesis of sJIA. Moreover, IL-6 may be the biomarker associated with arthritis in early JIA stage. Both autoinflammation and autoimmune response may be involved in the pathogenesis of sJIA. IL-17 enrichment may only occur in local joint, the levels of IL-17 in PB may not be significantly increased. The prominent expression gradient between SF and PB of IP-10 maybe the basis of performing chemotaxis and further causing joint damage.