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.
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.
Life Sci. 2020 Dec 1;262:118505. doi: 10.1016/j.lfs.2020.118505. Epub 2020 Sep 28.
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.
研究紫杉醇对脂多糖（LPS）诱导的急性肾损伤（AKI）的影响及其相关机制。
使用 LPS 诱导 HK-2 细胞建立脓毒症相关 AKI 模型。然后，分别通过 qRT-PCR 和 Western blot 分析检测 LPS 诱导 AKI 前后脓毒症患者血清和 HK-2 细胞中相关基因的 mRNA 和蛋白表达水平。随后，通过细胞计数试剂盒-8（CCK-8）和流式细胞术评估紫杉醇、lnc-MALAT1、miR-370-3p 和 HMGB1 对 LPS 损伤的 HK-2 细胞增殖和凋亡的影响。
lnc-MALAT1 在脓毒症患者血清和 LPS 损伤的细胞中均增加，可抑制细胞增殖，促进细胞凋亡，并增加紫杉醇引起的 TNF-α、IL-6 和 IL-1β 的表达。此外，lnc-MALAT1 与 miR-370-3p 结合，后者在 LPS 诱导的 HK-2 细胞中与 lnc-MALAT1 具有相反的作用。此外，miR-370-3p 靶向 HMGB1，HMGB1 在脓毒症患者血清和细胞中被诱导。miR-370-3p 的敲低抑制了 LPS 损伤的 HK-2 细胞中 HMGB1 的表达，抑制了细胞增殖，促进了细胞凋亡，并抑制了 TNF-α、IL-6 和 IL-1β 的表达。此外，紫杉醇通过调节 lnc-MALAT1/miR-370-3p 轴来抑制 HMGB1 的表达。
紫杉醇通过调节 lnc-MALAT1/miR-370-3p/HMGB1 轴和 TNF-α、IL-6 和 IL-1β 的表达，对 LPS 诱导的 AKI 具有保护作用，提示紫杉醇可能作为一种治疗药物，减少脓毒症相关 AKI。
