Paclitaxel alleviates the sepsis-induced acute kidney injury via lnc-MALAT1/miR-370-3p/HMGB1 axis

• Published in: Life sciences (1973) 2020-12, Vol.262, p.118505-118505, Article 118505
• Main Authors: Xu, Lina, Hu, Guyong, Xing, Pengcheng, Zhou, Minjie, Wang, Donglian
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Acute Kidney Injury - etiology; Acute Kidney Injury - prevention & control; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Cell Line; Cell Proliferation - drug effects; Chinese traditional medicine; Epithelial Cells - cytology; Epithelial Cells - pathology; HMGB1; HMGB1 Protein - genetics; Humans; Interleukin-1beta - genetics; Interleukin-6 - genetics; Kidney Tubules - cytology; Kidney Tubules - pathology; Lipopolysaccharides; lnc-MALAT1; MicroRNAs - genetics; miR-370-3p; Paclitaxel - pharmacology; RNA, Long Noncoding - genetics; Sepsis; Sepsis - complications; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118505

To investigate the effects of paclitaxel on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its related mechanisms. The sepsis-associated AKI was induced by LPS using HK-2 cells. Then the mRNA and protein expression levels of relevant genes in the serum of sepsis patients and HK-2 cells with LPS-induced AKI were detected by qRT-PCR and western blot analyses before and after paclitaxel treatment, respectively. Subsequently, the cell counting kit-8 (CCK-8) and flow cytometry assays were performed to estimate the effects of paclitaxel, lnc-MALAT1, miR-370-3p and HMGB1 on the proliferation and apoptosis of HK-2 cells injured by LPS. Lnc-MALAT1 was increased both in the serum of sepsis patients and cells injured by LPS, which could inhibit the cell proliferation, promote the cell apoptosis and increase the expression of TNF-α, IL-6 and IL-1β caused by paclitaxel. Moreover, lnc-MALAT1 was sponged with miR-370-3p which had the inverse effects with lnc-MALAT1 in LPS induced HK-2 cells. What's more, miR-370-3p targeted HMGB1 which was induced in serum and cells of sepsis. Knockdown of miR-370-3p inhibited the expression of HMGB1 and suppressed the proliferation but promoted the apoptosis of HK-2 cells injured by LPS as well as the expression of TNF-α, IL-6 and IL-1β. Besides, paclitaxel restrained the expression of HMGB1 via regulating lnc-MALAT1/miR-370-3p axis. Paclitaxel could protect against LPS-induced AKI via the regulation of lnc-MALAT1/miR-370-3p/HMGB1 axis and the expression of TNF-α, IL-6 and IL-1β, revealing that paclitaxel might act as a therapy drug in reducing sepsis-associated AKI. •Paclitaxel protected against LPS-induced AKI.•Lnc-MALAT1 was increased and influence the cell progression, and increased the expression of inflammatory factors caused by paclitaxel.•Lnc-MALAT1 sponged with miR-370-3p while miR-370-3p targeted HMGB1 which might be the reason for the effects of paclitaxel.•Paclitaxel played the role in sepsis-induced AKI via the regulation of TNF-α, IL-6 and IL-1β.