Klotho对滋养细胞侵袭的影响
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摘要
目的:研究Klotho对绒膜外滋养细胞系HTR8/SVneo侵袭的影响。方法:用免疫组化检测子痫前期及正常孕妇胎盘组织Klotho蛋白表达情况。实验分组为对照组、Klotho重组蛋白组、Klotho siRNA组。Transwell小室法检测侵袭能力,Western Blot检测细胞蛋白表达水平。结果:子痫前期胎盘组织Klotho表达水平明显低于正常胎盘组织。Klotho重组蛋白处理细胞后,HTR8/SVneo细胞侵袭能力显著增强、其表达的基质金属蛋白酶2(MMP-2)及基质金属蛋白酶9(MMP-9)表达上调。Klotho siRNA处理细胞后,HTR8/SVneo细胞侵袭能力显著减弱、其表达的MMP-2及MMP-9表达显著下调。结论:Klotho可能通过介导MMP-2和MMP-9的表达调节滋养细胞侵袭能力,为子痫前期发病机制的研究提供了新线索。
Objective: To investigate the effect of Klotho on invasion of Extrachorionic trophoblastic cell line HTR-8/SVneo cells. Methods: Klotho protein expression in placenta of preeclampsia and normal pregnant women was detected by immunohistochemistry. Experimental grouping: Normal control group, Klotho recombinant protein group, Klotho SiRNA group. The abilities of cell were measured by Transwell assay. The protein expression were detected by Western blot. Results: The expression of Klotho in placenta of preeclampsia was significantly lower than that in normal placenta. Treatment with Klotho recombinant protein improved the HTR-8/SVneo cell invasion abilities, and upregulated the expression of MMP-2 and MMP-9. The effects were re-versed by treatment with Klotho siRNA. Conclusion: Klotho regulate the invasion of trophoblast may via MMP-2 and MMP-9 expression. It provides a new clue for the study of the pathogenesis of preeclampsia.
Objective: To investigate the effect of Klotho on invasion of Extrachorionic trophoblastic cell line HTR-8/SVneo cells. Methods: Klotho protein expression in placenta of preeclampsia and normal pregnant women was detected by immunohistochemistry. Experimental grouping: Normal control group, Klotho recombinant protein group, Klotho SiRNA group. The abilities of cell were measured by Transwell assay. The protein expression were detected by Western blot. Results: The expression of Klotho in placenta of preeclampsia was significantly lower than that in normal placenta. Treatment with Klotho recombinant protein improved the HTR-8/SVneo cell invasion abilities, and upregulated the expression of MMP-2 and MMP-9. The effects were re-versed by treatment with Klotho siRNA. Conclusion: Klotho regulate the invasion of trophoblast may via MMP-2 and MMP-9 expression. It provides a new clue for the study of the pathogenesis of preeclampsia.
引文
1 Jim B,Karumanchi SA.Preeclampsia:Pathogenesis,prevention,and long-term complications[J].Semin Nephrol,2017,37(4):386-397.
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4 Park MY,Herrmann SM,Saad A,et al.Biomarkers of kidney injury and Klotho in patients with atherosclerotic renovascular disease[J].Clin J Am Soc Nephrol,2015,10(3):443-451.
5 Xie B,Nie S,Hu G,et al.The involvement of NF-kappaB/Klotho signaling in colorectal cancer cell survival and invasion[J].Pathol Oncol Res,2019.
6 Skovsted GF,Tveden-Nyborg P,Lykkesfeldt J.Expression of endothelin type B receptors in uterine artery smooth muscle cells from pregnant Guinea pigs[J].Placenta,2019,77:8-15.
7 Chaiworapongsa T,Chaemsaithong P,Yeo L,et al.Pre-eclampsia part 1:current understanding of its pathophysiology[J].Nat Rev Nephrol,2014,10(8):466-480.
8 Mao S,Wang X,Wu L,et al.Association between Klotho expression and malignancies risk and progression:A meta-analysis[J].Clin Chim Acta,2018,484:14-20.
9 Xie B,Cao K,Li J,et al.Hmgb1 inhibits Klotho expression and malignant phenotype in melanoma cells by activating NF-kappaB[J].Oncotarget,2016,7(49):80765-80782.
10 Li P,Zhao M,Qi X,et al.Downregulation of Klotho beta is associated with invasive ductal carcinoma progression[J].Oncol Lett,2017,14(6):7443-7448.
11 Arbel RT,Shahmoon S,Zigmond E,et al.Klotho suppresses colorectal cancer through modulation of the unfolded protein response[J].Oncogene,2019,38(6):794-807.
12 Fakhar M,Najumuddin,Gul M,et al.Antagonistic role of Klotho-derived peptides dynamics in the pancreatic cancer treatment through obstructing WNT-1 and Frizzled binding[J].Biophys Chem,2018,240:107-117.
13 Chen B,Liang Y,Chen L,et al.Overexpression of Klotho inhibits HELF fibroblasts SASP-related protumoral effects on non-small cell lung cancer cells[J].J Cancer,2018,9(7):1248-1258.
14 Lombardi A,Makieva S,Rinaldi SF,et al.Expression of matrix metalloproteinases in the mouse uterus and human myometrium during pregnancy,labor,and preterm labor[J].Reprod Sci,2018,25(6):938-949.
15 Espino YSS,Flores-Pliego A,Espejel-Nunez A,et al.New insights into the role of matrix metalloproteinases in preeclampsia[J].Int J Mol Sci,2017,18(7).
2 Ngene NC,Moodley J.Role of angiogenic factors in the pathogenesis and management of pre-eclampsia[J].Int J Gynaecol Obstet,2017.
3 Imura A,Iwano A,Tohyama O,et al.Secreted Klotho protein in sera and CSF:implication for post-translational cleavage in release of Klotho protein from cell membrane[J].FEBS Lett,2004,565(1-3):143-147.
4 Park MY,Herrmann SM,Saad A,et al.Biomarkers of kidney injury and Klotho in patients with atherosclerotic renovascular disease[J].Clin J Am Soc Nephrol,2015,10(3):443-451.
5 Xie B,Nie S,Hu G,et al.The involvement of NF-kappaB/Klotho signaling in colorectal cancer cell survival and invasion[J].Pathol Oncol Res,2019.
6 Skovsted GF,Tveden-Nyborg P,Lykkesfeldt J.Expression of endothelin type B receptors in uterine artery smooth muscle cells from pregnant Guinea pigs[J].Placenta,2019,77:8-15.
7 Chaiworapongsa T,Chaemsaithong P,Yeo L,et al.Pre-eclampsia part 1:current understanding of its pathophysiology[J].Nat Rev Nephrol,2014,10(8):466-480.
8 Mao S,Wang X,Wu L,et al.Association between Klotho expression and malignancies risk and progression:A meta-analysis[J].Clin Chim Acta,2018,484:14-20.
9 Xie B,Cao K,Li J,et al.Hmgb1 inhibits Klotho expression and malignant phenotype in melanoma cells by activating NF-kappaB[J].Oncotarget,2016,7(49):80765-80782.
10 Li P,Zhao M,Qi X,et al.Downregulation of Klotho beta is associated with invasive ductal carcinoma progression[J].Oncol Lett,2017,14(6):7443-7448.
11 Arbel RT,Shahmoon S,Zigmond E,et al.Klotho suppresses colorectal cancer through modulation of the unfolded protein response[J].Oncogene,2019,38(6):794-807.
12 Fakhar M,Najumuddin,Gul M,et al.Antagonistic role of Klotho-derived peptides dynamics in the pancreatic cancer treatment through obstructing WNT-1 and Frizzled binding[J].Biophys Chem,2018,240:107-117.
13 Chen B,Liang Y,Chen L,et al.Overexpression of Klotho inhibits HELF fibroblasts SASP-related protumoral effects on non-small cell lung cancer cells[J].J Cancer,2018,9(7):1248-1258.
14 Lombardi A,Makieva S,Rinaldi SF,et al.Expression of matrix metalloproteinases in the mouse uterus and human myometrium during pregnancy,labor,and preterm labor[J].Reprod Sci,2018,25(6):938-949.
15 Espino YSS,Flores-Pliego A,Espejel-Nunez A,et al.New insights into the role of matrix metalloproteinases in preeclampsia[J].Int J Mol Sci,2017,18(7).