Knockdown of LncRNA DLX6-AS1 inhibits HK-2 cell pyroptosis via regulating miR-223-3p/NLRP3 pathway in lipopolysaccharide
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Knockdown of LncRNA DLX6-AS1 inhibits HK-2 cell pyroptosis via regulating miR-223-3p/NLRP3 pathway in lipopolysaccharide-induced acute kidney injury Jixiang Tan 1 & Jing Fan 1 & Jin He 2 & Lin Zhao 1 & Hongjun Tang 1 Received: 15 March 2020 / Accepted: 10 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Sepsis-induced acute kidney injury (AKI) represents a severe medical complication. Recently, there is growing evidence indicating the regulatory role of long non-coding RNAs (lncRNAs) in AKI pathophysiology. The present study investigated lncRNA DLX6 antisense RNA 1 (DLX6-AS1) expression in septic AKI patients and to decipher the relevant mechanisms underlying DLX6-AS1-mediated HK-2 cell pyroptosis in lipopolysaccharide (LPS)-induced AKI. The results revealed that DLX6-AS1 was up-regulated in the serum from septic AKI patients. DLX6-AS1 expression were positively associated with the creatinine levels in the serum from the septic AKI patients. In vitro studies showed that LPS induced cytotoxicity and enhanced DLX6-AS1 expression of HK-2 cells; increased NLR family pyrin domain containing 3 (NLRP3), interleukin (IL)-1β and IL-18 expression. DLX6-AS1 overexpression promoted cytotoxicity and pyroptosis of HK-2 cells; while DLX6-AS1 knockdown counteracted the LPS-induced cytotoxicity and pyroptosis of HK-2 cells. More importantly, DLX6-AS1 sponged miR-223-3p resulting in repression of miR-223-3p expression in HK-2 cells. MiR-223-3p could bind to the 3′ untranslated region of NLRP3, which results in the suppressed NLRP3 expression of HK-2 cells. Further rescue experiments showed that enhanced miR-223-3p expression partially reversed the cytotoxicity and pyroptosis of HK-2 cells upon LPS stimulation or with DLX6-AS1 overexpression. Conclusively, this study identified enhanced DLX6-AS1 expression in the serum from AKI patients. Further mechanistic findings deciphered that DLX6-AS1 mediated LPS-mediated cytotoxicity and pyroptosis in HK-2 via miR-223-3p/NLRP3 axis. Keywords Sepsis-induced AKI . DLX6-AS1 . Lipopolysaccharide . Pyroptosis . miR-223-3p . NLRP3
Introduction Sepsis is a disease with severe inflammation, and sepsis is featured by a systemic inflammatory response (Godin et al. 2015). According to the clinical evidence, sepsis is mainly caused by trauma, abdominal surgery or hemorrhage (Godin et al. 2015). Acute kidney injury (AKI) represents a severe and fatal complication in sepsis
progression, and studies have found that severe sepsis could cause about 50% of the cases of AKI (HummekeOppers et al. 2019; Peerapornratana et al. 2019). Though great improvements have been made for treating sepsisinduced AKI, effective prognosis and detailed pathophysiology of sepsis-induced AKI remain elusive (HummekeOppers et al. 2019; Peerapornratana et al. 2019). Thus, there is an urgent need for us to further explore the
* Lin Zhao [email protected] Jixiang Tan [email protected] Jing Fan [email protected] Jin He [email protected]
Hongjun Tang [email protected] 1
Department of Eme
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