Open AccessLnc RNA Tap SAKI promotes inflammation injury in HK ‐2 cells and urine derived sepsis‐induced kidney injury
Author(s) -
Shen Jun,
Liu Li,
Zhang Facai,
Gu Jiang,
Pan Guanghui
Publication year - 2019
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13049
Subject(s) - pten , tlr4 , apoptosis , gene knockdown , kidney , acute kidney injury , western blot , inflammation , in vivo , sepsis , cancer research , chemistry , pi3k/akt/mtor pathway , biology , medicine , endocrinology , biochemistry , gene , microbiology and biotechnology
Objective To explore the possible mechanism of lnc RNA Tap SAKI in urine derived sepsis‐induced kidney injury. Materials and methods In vivo urine‐derived sepsis ( US ) rat model and in vitro LPS ‐induced HK ‐2 cells were established, and Tap SAKI , miR‐22, PTEN , TLR 4 and p‐p65 expressions were detected by qRT ‐ PCR and western blot. RNA precipitation and RNA pull‐down were performed to confirm the interaction between Tap SAKI and miR‐22. Results Tap SAKI was up‐regulated, miR‐22 was down‐regulated, PTEN , TLR 4 and p‐p65 expressions, and inflammatory factors TNF ‐α and IL ‐6 levels were up‐regulated in kidney tissue of US rats and LPS ‐induced HK ‐2 cells. In addition, Tap SAKI interacted with miR‐22, and negatively modulate miR‐22 expression. We also observed Tap SAKI promoted PTEN expression, TLR 4/ NF ‐κB pathway related proteins TLR 4 and p‐p65, and apoptosis protein cleaved‐caspase‐3 through negatively regulating miR‐22. Further experiments proved Tap SAKI /miR‐22/ TLR 4/ NF ‐κB pathway could promote HK ‐2 cell apoptosis. Finally, i n vivo experiments showed Tap SAKI knockdown negatively regulated miR‐22 and positively regulate PTEN , decreased renal function indicators blood urea nitrogen and serum creatinine, and reduced TNF ‐α and IL ‐6. Conclusion Tap SAKI was elevated in urine derived sepsis‐induced kidney injury, and promoted HK ‐2 cell apoptosis and inflammatory response through miR‐22/ PTEN / TLR 4/ NF ‐κB pathway.