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Mechanism of p38MAPK
signaling pathway mediating miR-21 in renal ischemia-reperfusion injury
LIU Lianhong, LI Zhihui
2021, 13 (6):
468-472.
doi: 10.3969/j.issn.1674-3865.2021.06.003
Objective To study the
functioning mechanism of microRNA-21（miR-21） and p38MAPK signaling pathway in renal injury of ischemia
reperfusion(IR).Methods Male C57BL/6J mice were divided into four groups based
on whether IR was performed: blank control group, IR group, sham operation
group and ischemia preconditioning+ischemia reperfusion group (IPC+IR
group).Then they were each divided to 8 subgroups according to different time
points after IR（0min，5min, 30min, 45min, 2h, 12h, 24h, 48h）. Analyze the renal
tissue, miR-21 level, expression
level of p38MAPK and p-p38MAPK protein, and
pathological injury of kidney.Results (1)Pathology of kidney：there was no obvious
renal injury in the blank control group;pathology injury of kidney gradually
appeared after IR in IR group and sham-operation group, which peaked at 24h and gradually recovered; after ischemic
preconditioning, the tendency of pathological injury of kidney in IPC+IR group
was parallel to that in IR group, but the injury of each subgroup was milder
than IR group, and there was statistical difference in the score of renal tubular
pathological injury between IPC+IR group and IR and sham-operation group（P<0.01）. (2)p38MAPK expression level: there was no statistical difference in
the relative expression level(p-p38MAPK/β-actin） among the groups at
the 8 time points(P>0.05). (3)The relative expression level of p-p38MAPK(p-p38MAPK/p38MAPK):there
was no obvious expression in blank control group; in IR group, the relative
expression level of p-p38MAPK increased
rapidly at 15min after IR and peaked at 2h, and remained at a relatively high
level afterwards.After ischemic preconditioning, the tendency of the relative
expression level of p-p38MAPK in IPC+IR
group was parallel to that in IR group,and the level peaked at 2h, but it was
lower in each of the 8 subgroups than in the IR group and sham-operation group, the difference being statistical（P<0.01）.（4）Expression level of
miR-21:in IR group, with
time passing, miR-21 expression
increased at 5min after IR and peaked at 24h,being 15.2 times that of baseline,
and remained at a relatively high level, while there was no obvious change in
miR-21 expression level
in blank control group. After ischemic preconditioning,in IPC+IR group,
the expression level of miR-21 remained at the peak level of the IR group at each time points within
48h, which was about 14.8 times that of that of the baseline level,and there
was statistical difference between IPC+IR group and sham-operation and IR group（P<0.01）.Conclusion The possible mechanism of ischemic preconditioning in
protecting kidney may be to upregulate miR-21 and inhibit the phosphorylation of p38MAPK in order to reduce the
expression of the related downstream inflammatory mediators of p38MAPK
signaling pathway.
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