Lina Xu1, Guyong Hu2, Pengcheng Xing3, Minjie Zhou2, Donglian Wang2. 1. Department of Infectious Diseases, Shanghai University of Medicine & Health Sciences Affiliated Shanghai Sixth People's Hospital East, No. 222, West Three Road Around Lake, Pudong District, Shanghai 201306, PR China. 2. Department of Emergency, Shanghai University of Medicine & Health Sciences Affiliated Shanghai Sixth People's Hospital East, No. 222, West Three Road Around Lake, Pudong District, Shanghai 201306, PR China. 3. Department of Emergency, Shanghai University of Medicine & Health Sciences Affiliated Shanghai Sixth People's Hospital East, No. 222, West Three Road Around Lake, Pudong District, Shanghai 201306, PR China. Electronic address: xingpengchengdoc@aliyun.com.
Abstract
AIMS: To investigate the effects of paclitaxel on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its related mechanisms. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: To investigate the effects of paclitaxel on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and its related mechanisms. MAIN METHODS: 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 sepsispatients 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. KEY FINDINGS: Lnc-MALAT1 was increased both in the serum of sepsispatients 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. SIGNIFICANCE: 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.