Jun Shen1, Junhao Zhang2, Xinan Jiang2, Huan Wang3, Guanghui Pan4. 1. Department of Organ Transplantation, The Affiliated Hospital, Guizhou Medical University, Guiyang 550004, China. Electronic address: sur_geon@yahoo.com. 2. Department of Urology, The Affiliated Hospital, Guizhou Medical University, Guiyang 550004, China. 3. Department of Human Anatomy & Histoembryology, School of Basic Medical, Guizhou Medical University, Guiyang 550025, China. 4. Department of Organ Transplantation, The Affiliated Hospital, Guizhou Medical University, Guiyang 550004, China.
Abstract
OBJECTIVE: This study investigated the role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in kidney injury induced by urine-derived sepsis (US). MATERIALS AND METHODS: An Escherichia coli suspension was injected into the distal ureter of adult male Sprague Dawley rats to establish a US model. Lipopolysaccharides (LPSs) were used to induce an in vitro septic model. The interaction between HOTAIR and microRNA 22 (miR-22) was detected by RNA precipitation and RNA pull-down assays. The expression of HOTAIR, miR-22, and high mobility group box 1 (HMGB1) were detected by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot analyses. RESULTS: Compared with a sham group, HOTAIR was upregulated in kidney tissues of the US group. HOTAIR was also upregulated in LPS-induced human renal tubular epithelial cells (HK-2). Furthermore, HOTAIR negatively regulated miR-22 and promoted apoptosis of HK-2 cells. HOTAIR also promoted HMGB1 expression and HK-2 cell apoptosis by inhibiting miR-22. In addition, the miR-22/HMGB1 pathway was involved in LPS-induced HK-2 cell apoptosis. In vivo experiments showed that HOTAIR negatively modulated miR-22 and positively modulated HMGB1 and that HOTAIR knockdown decreased renal function indicators (blood urea nitrogen [BUN] and serum creatinine). CONCLUSION: HOTAIR was upregulated in sepsis-induced kidney injury, which promoted HK-2 cell apoptosis in kidney injury through the miR-22/HMGB1 pathway.
OBJECTIVE: This study investigated the role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in kidney injury induced by urine-derived sepsis (US). MATERIALS AND METHODS: An Escherichia coli suspension was injected into the distal ureter of adult male Sprague Dawley rats to establish a US model. Lipopolysaccharides (LPSs) were used to induce an in vitro septic model. The interaction between HOTAIR and microRNA 22 (miR-22) was detected by RNA precipitation and RNA pull-down assays. The expression of HOTAIR, miR-22, and high mobility group box 1 (HMGB1) were detected by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot analyses. RESULTS: Compared with a sham group, HOTAIR was upregulated in kidney tissues of the US group. HOTAIR was also upregulated in LPS-induced human renal tubular epithelial cells (HK-2). Furthermore, HOTAIR negatively regulated miR-22 and promoted apoptosis of HK-2 cells. HOTAIR also promoted HMGB1 expression and HK-2 cell apoptosis by inhibiting miR-22. In addition, the miR-22/HMGB1 pathway was involved in LPS-induced HK-2 cell apoptosis. In vivo experiments showed that HOTAIR negatively modulated miR-22 and positively modulated HMGB1 and that HOTAIR knockdown decreased renal function indicators (blood ureanitrogen [BUN] and serum creatinine). CONCLUSION:HOTAIR was upregulated in sepsis-induced kidney injury, which promoted HK-2 cell apoptosis in kidney injury through the miR-22/HMGB1 pathway.
Authors: Seyed MohammadReza Hashemian; Mohammad Hossein Pourhanifeh; Sara Fadaei; Ali Akbar Velayati; Hamed Mirzaei; Michael R Hamblin Journal: Mol Ther Nucleic Acids Date: 2020-05-15 Impact factor: 8.886