nach oben

Inflammation

Erschienen in:

02.04.2018 | ORIGINAL ARTICLE

Geniposide Attenuates LPS-Induced Injury via Up-Regulation of miR-145 in H9c2 Cells

verfasst von: Qiang Su, Junjing Yao, Cunjian Sheng

Erschienen in: Inflammation | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Myocarditis is a cardiomyopathy associated with inflammatory response. It has been reported that geniposide (GEN), a traditional Chinese herb extract from Gardenia jasminoides Ellis, possesses an anti-inflammatory effect and a protective effect on cardiomyocytes. The present study aimed to explore the protective role of GEN and the underlying mechanism in LPS-injured H9c2 cells. H9c2 cells were treated with LPS to induce cell injury and then we investigated the effect of GEN. miR-145 expression was inhibited by transfection with miR-145 inhibitor and its expression was measured by RT-PCR. Cell viability and apoptotic cells were measured by CCK-8 assay and flow cytometry analysis. The levels of pro-inflammatory factors (IL-6, TNF-α, and MCP-1) were assessed by western blot and RT-PCR. Western blot was performed to detect the expression of the MEK/ERK pathway-related factors. LPS exposure reduced cell viability, increased apoptotic cells, and promoted the expression of pro-inflammatory factors in H9c2 cells. However, GEN pretreatment significantly reduced LPS-induced cell injury, as increased cell viability, reduced apoptotic cells, and inhibited the expression of pro-inflammatory factors. Moreover, we found that miR-145 expression was down-regulated by LPS exposure but was up-regulated by GEN pretreatment. The protective effect of GEN on LPS-injured H9c2 cells was blocked by miR-145 inhibitor. In addition, GEN inhibited the MEK/ERK pathway through up-regulating miR-145. Our results suggested that GEN exerted a protective role in LPS-injured H9c2 cells. The GEN-associated regulation might be related to its regulation on miR-145 and the MEK/ERK signaling pathway.

Banerjee, Aditya, Aryadeep Roychoudhury, and S. Krishnamoorthi. 2016. Emerging techniques to decipher microRNAs (miRNAs) and their regulatory role in conferring abiotic stress tolerance of plants. Plant Biotechnology Reports 10 (4): 185–205.CrossRef

Basso, C., F. Calabrese, A. Angelini, E. Carturan, and G. Thiene. 2013. Classification and histological, immunohistochemical, and molecular diagnosis of inflammatory myocardial disease. Heart Failure Reviews 18 (6): 673–681.CrossRefPubMed

Chiyomaru, T., H. Enokida, S. Tatarano, K. Kawahara, Y. Uchida, K. Nishiyama, L. Fujimura, N. Kikkawa, N. Seki, and M. Nakagawa. 2010. miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. British Journal of Cancer 102 (5): 883–891. https://doi.org/10.1038/sj.bjc.6605570.CrossRefPubMedPubMedCentral

Cho, W.C., A.S. Chow, and J.S. Au. 2009. Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation. European Journal of Cancer 45 (12): 2197–2206. https://doi.org/10.1016/j.ejca.2009.04.039.CrossRefPubMed

Coggins, M., and A. Rosenzweig. 2012. The fire within: cardiac inflammatory signaling in health and disease. Circulation Research 110 (1): 116–125.CrossRefPubMed

Dong, Maolong, Nan Hu, Yinan Hua, Xihui Xu, Machender R. Kandadi, Rui Guo, Shasha Jiang, Sreejayan Nair, Dahai Hu, and Jun Ren. 2013. Chronic Akt activation attenuated lipopolysaccharide-induced cardiac dysfunction via Akt/GSK3β-dependent inhibition of apoptosis and ER stress. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1832 (6): 848–863. https://doi.org/10.1016/j.bbadis.2013.02.023.CrossRef

Higashi, K., Y. Yamada, S. Minatoguchi, S. Baba, M. Iwasa, H. Kanamori, M. Kawasaki, K. Nishigaki, G. Takemura, M. Kumazaki, Y. Akao, and S. Minatoguchi. 2015. MicroRNA-145 repairs infarcted myocardium by accelerating cardiomyocyte autophagy. American Journal of Physiology. Heart and Circulatory Physiology 309 (11): H1813–H1826. https://doi.org/10.1152/ajpheart.00709.2014. CrossRefPubMed

Hua, Fang, Tuanzhu Ha, Jing Ma, Yan Li, Jim Kelley, Xiang Gao, I. William Browder, Race L. Kao, David L. Williams, and Chuanfu Li. 2007. Protection against myocardial ischemia/reperfusion injury in TLR4-deficient mice is mediated through a phosphoinositide 3-kinase-dependent mechanism. The Journal of Immunology 178 (11): 7317–7324. https://doi.org/10.4049/jimmunol.178.11.7317.CrossRefPubMed

Jiang, Y.Q., G.L. Chang, Y. Wang, D.Y. Zhang, L. Cao, and J. Liu. 2016. Geniposide prevents hypoxia/reoxygenation-induced apoptosis in H9c2 cells: improvement of mitochondrial dysfunction and activation of GLP-1R and the PI3K/AKT signaling pathway. Cellular Physiology and Biochemistry 39 (1): 407–421. https://doi.org/10.1159/000445634.CrossRefPubMed

10.

Kano, M., N. Seki, N. Kikkawa, L. Fujimura, I. Hoshino, Y. Akutsu, T. Chiyomaru, H. Enokida, M. Nakagawa, and H. Matsubara. 2010. miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. International Journal of Cancer 127 (12): 2804–2814. https://doi.org/10.1002/ijc.25284.CrossRefPubMed

11.

Li, D.W., J.P. Liu, Y.W. Mao, H. Xiang, J. Wang, W.Y. Ma, Z. Dong, H.M. Pike, R.E. Brown, and J.C. Reed. 2005. Calcium-activated RAF/MEK/ERK signaling pathway mediates p53-dependent apoptosis and is abrogated by alpha B-crystallin through inhibition of RAS activation. Molecular Biology of the Cell 16 (9): 4437–4453.CrossRefPubMedPubMedCentral

12.

Li, F., W. Li, X. Li, F. Li, L. Zhang, B. Wang, G. Huang, X. Guo, L. Wan, Y. Liu, S. Zhang, S. Kang, and J. Ma. 2016. Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells. Journal of Ethnopharmacology 185: 77–86. https://doi.org/10.1016/j.jep.2016.03.025. CrossRefPubMed

13.

Li, R., G. Yan, Q. Li, H. Sun, Y. Hu, J. Sun, and B. Xu. 2012. MicroRNA-145 protects cardiomyocytes against hydrogen peroxide (H2O2)-induced apoptosis through targeting the mitochondria apoptotic pathway. PLoS One 7 (9): e44907.CrossRefPubMedPubMedCentral

14.

Li, R., G. Yan, Q. Zhang, Y. Jiang, H. Sun, Y. Hu, J. Sun, and B. Xu. 2013. miR-145 inhibits isoproterenol-induced cardiomyocyte hypertrophy by targeting the expression and localization of GATA6. FEBS Letters 587 (12): 1754–1761. https://doi.org/10.1016/j.febslet.2013.04.018.CrossRefPubMedPubMedCentral

15.

Lin, Chien-Hung, and Chung-Ching Lin. 2016. Sitagliptin attenuates inflammatory responses in lipopolysaccharide-stimulated cardiomyocytes via nuclear factor-κB pathway inhibition. Experimental and Therapeutic Medicine 11 (6): 2609–2615. https://doi.org/10.3892/etm.2016.3255.CrossRefPubMedPubMedCentral

16.

Liu, J.H., F. Yin, L.X. Guo, X.H. Deng, and Y.H. Hu. 2009. Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway. Acta Pharmacologica Sinica 30 (2): 159–165. https://doi.org/10.1038/aps.2008.25.CrossRefPubMedPubMedCentral

17.

Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25 (4): 402–408.CrossRefPubMed

18.

Maddahi, A., and L. Edvinsson. 2010. Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway. Journal of Neuroinflammation 7: 14. https://doi.org/10.1186/1742-2094-7-14.CrossRefPubMedPubMedCentral

19.

Pan, Li-Long, Xin-Hua Liu, Qi-Hai Gong, and Yi-Zhun Zhu. 2011. S-Propargyl-cysteine (SPRC) attenuated lipopolysaccharide-induced inflammatory response in H9c2 cells involved in a hydrogen sulfide-dependent mechanism. Amino Acids 41 (1): 205–215. https://doi.org/10.1007/s00726-011-0834-1.CrossRefPubMed

20.

Parthasarathy, G., and M.T. Philipp. 2014. The MEK/ERK pathway is the primary conduit for Borrelia burgdorferi-induced inflammation and P53-mediated apoptosis in oligodendrocytes. Apoptosis 19 (1): 76–89. https://doi.org/10.1007/s10495-013-0913-8.CrossRefPubMedPubMedCentral

21.

Peng, C.H., C.N. Huang, S.P. Hsu, and C.J. Wang. 2007. Penta-acetyl geniposide-induced apoptosis involving transcription of NGF/p75 via MAPK-mediated AP-1 activation in C6 glioma cells. Toxicology 238 (2–3): 130–139. https://doi.org/10.1016/j.tox.2007.05.029.CrossRefPubMed

22.

Pollack, A., A.R. Kontorovich, V. Fuster, and G.W. Dec. 2015. Viral myocarditis—diagnosis, treatment options, and current controversies. Nature Reviews Cardiology 12 (11): 670–680.CrossRefPubMed

23.

Robinson, Emma, Roslyn S. Cassidy, Mitchel Tate, Youyou Zhao, Samuel Lockhart, Danielle Calderwood, Rachel Church, et al. 2015. Exendin-4 protects against post-myocardial infarction remodelling via specific actions on inflammation and the extracellular matrix. Basic Research in Cardiology 110 (2): 20. https://doi.org/10.1007/s00395-015-0476-7.CrossRefPubMedPubMedCentral

24.

Rong, Y.P., H.T. Huang, J.S. Liu, and L. Wei. 2017. Protective effects of geniposide on hepatic ischemia/reperfusion injury. Transplantation Proceedings 49 (6): 1455–1460. https://doi.org/10.1016/j.transproceed.2017.02.063.CrossRefPubMed

25.

Sachdeva, M., S. Zhu, F. Wu, H. Wu, V. Walia, S. Kumar, R. Elble, K. Watabe, and Y.Y. Mo. 2009. p53 represses c-Myc through induction of the tumor suppressor miR-145. Proceedings of the National Academy of Sciences of the United States of America 106 (9): 3207–3212.CrossRefPubMedPubMedCentral

26.

Sandeep, Sagar, Peter P. Liu, and Leslie T. Cooper. 2012. Myocarditis. Lancet 379 (9817): 738–747.CrossRef

27.

Song, X., W. Zhang, T. Wang, H. Jiang, Z. Zhang, Y. Fu, Z. Yang, Y. Cao, and N. Zhang. 2014. Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice. Inflammation 37 (5): 1588–1598. https://doi.org/10.1007/s10753-014-9885-2.CrossRefPubMed

28.

Wang, R., and H. Wu. 2017. Antiinflammation effects and mechanisms study of geniposide on rats with collagen-induced arthritis. 31 (4):631–637. doi: 10.1002/ptr.5775.

29.

Wang, Z., X. Zhang, Z. Yang, H. Du, Z. Wu, J. Gong, J. Yan, and Q. Zheng. 2012. MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells. Biochemical & Biophysical Research Communications 427 (3): 444–449.CrossRef

30.

Wu, S.Y., G.F. Wang, Z.Q. Liu, J.J. Rao, L. Lu, W. Xu, S.G. Wu, and J.J. Zhang. 2009. Effect of geniposide, a hypoglycemic glucoside, on hepatic regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin. Acta Pharmacologica Sinica 30 (2): 202–208. https://doi.org/10.1038/aps.2008.17.CrossRefPubMedPubMedCentral

31.

Yong, L.U., Michael Chopp, Xuguang Zheng, Mark Katakowski, Benjamin Buller, and Feng Jiang. 2013. MiR-145 reduces ADAM17 expression and inhibits in vitro migration and invasion of glioma cells. Oncology Reports 29 (1): 67–72.CrossRef

32.

Yuan, Ming, Liwei Zhang, Fei You, Jingyu Zhou, Yongjiang Ma, Feifei Yang, and Ling Tao. 2017. MiR-145-5p regulates hypoxia-induced inflammatory response and apoptosis in cardiomyocytes by targeting CD40. Molecular and Cellular Biochemistry 431 (1): 123–131. https://doi.org/10.1007/s11010-017-2982-4.CrossRefPubMed

33.

Zhang, T., T. Yan, J. Du, S. Wang, and H. Yang. 2015. Apigenin attenuates heart injury in lipopolysaccharide-induced endotoxemic model by suppressing sphingosine kinase 1/sphingosine 1-phosphate signaling pathway. Chemico-Biological Interactions 233: 46–55. https://doi.org/10.1016/j.cbi.2014.12.021.CrossRefPubMed

34.

Zhang, Z., Z. Wang, H. Ren, M. Yue, K. Huang, H. Gu, M. Liu, B. Du, and M. Qian. 2011. P2Y(6) agonist uridine 5′-diphosphate promotes host defense against bacterial infection via monocyte chemoattractant protein-1-mediated monocytes/macrophages recruitment. Journal of Immunology 186 (9): 5376–5387. https://doi.org/10.4049/jimmunol.1002946.CrossRef

35.

Zhou, H., Y. Yuan, Y. Liu, J. Ni, W. Deng, Z.Y. Bian, J. Dai, and Q.Z. Tang. 2015. Icariin protects H9c2 cardiomyocytes from lipopolysaccharide-induced injury via inhibition of the reactive oxygen species-dependent c-Jun N-terminal kinases/nuclear factor-κB pathway. Molecular Medicine Reports 11 (6): 4327–4332.CrossRefPubMed

Titel: Geniposide Attenuates LPS-Induced Injury via Up-Regulation of miR-145 in H9c2 Cells
verfasst von: Qiang Su
Junjing Yao
Cunjian Sheng
Publikationsdatum: 02.04.2018
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 4/2018
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-018-0769-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2018

Saikosaponin A Inhibits LPS-Induced Endometritis in Mice Through Activating Nrf2 Signaling Pathway

Salicytamide: a New Anti-inflammatory Designed Drug Candidate

SOCS-1 Suppresses Inflammation Through Inhibition of NALP3 Inflammasome Formation in Smoke Inhalation-Induced Acute Lung Injury

CpG-ODNs and Budesonide Act Synergistically to Improve Allergic Responses in Combined Allergic Rhinitis and Asthma Syndrome Induced by Chronic Exposure to Ovalbumin by Modulating the TSLP-DC-OX40L Axis

NLRP3 Inflammasome Involves in the Acute Exacerbation of Patients with Chronic Obstructive Pulmonary Disease