Crocin ameliorates peritoneal fibrosis in rat induced by peritoneal dialysis via Wnt5a/β-Catenin pathway
Main Article Content
Keywords
crocin, peritoneal dialysis, peritoneal fibrosis, inflammation, Wnt5a/β-Catenin
Abstract
Peritoneal dialysis is used in the treatment of patients with kidney diseases. Long-term peritoneal dialysis could result in peritoneal fibrosis and recurrent peritonitis, thus leading to failure of ultrafiltration. Crocin is a bioactive carotenoid and isolated from stigma of Crocus sativus, and ameliorates pulmonary and myocardial fibrosis. The role of crocin in peritoneal fibrosis was assessed. Firstly, rats model with peritoneal dialysis was treated with 4.25% peritoneal dialysate. Results showed that injection with peritoneal dialysate induced obvious hyperplasia and increased thickness in peritoneum structure. Rats with peritoneal dialysis were injected with increasing concentrations of crocin at 10, 20, or 40 mg/kg. Crocin ameliorated the pathological changes in the peritoneum of peritoneal dialysate-induced rats. Secondly, crocin attenuated peritoneal dialysate-induced decrease of E-cadherin, increase of fibronectin, α-smooth muscle actin (α-SMA), and collagen I. Moreover, crocin enhanced ultrafiltration volume and reduced glucose transport in rats model with peritoneal dialysis. Thirdly, crocin also reduced levels of Interleukin (IL)-1β, Tumor Necrosis Factor-α (TNF –α), and IL-6 in peritoneal tissues of rats model with peritoneal dialysis. Lastly, protein expression of Wnt5a and β-Catenin in rats model with peritoneal dialysis were also downregulated by crocin. In conclusion, crocin exerted anti-inflammatory and anti-fibrotic effects on rats model with peritoneal dialysis through inactivation of Wnt5a/β-Catenin pathway.
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References
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Ruiqi, L., Ming, P., Qihang, S., Yangyang, L., Junli, C., Wei, L., Chao, G., Xinyue, L., Kang, Y. and Hongtao, Y., 2021. Saikosaponin D inhibits peritoneal fibrosis in rats with renal failure by regulation of TGFβ1/BMP7/Gremlin1/Smad pathway. Frontiers in Pharmacology 12: 628671. 10.3389/fphar.2021.628671
Tsuzuki, T., Iwata, H., Murase, Y., Takahara, T. and Ohashi, A., 2018. Renal tumors in end-stage renal disease: a comprehensive review. International Journal of Urology 25: 780–786. 10.1111/iju.13759
Vafaei, S., Wu, X., Tu, J. and Nematollahi-Mahani, S.N., 2022. The effects of crocin on bone and cartilage diseases. Frontiers in Pharmacology 12: 830331. 10.3389/fphar.2021.830331
van baal, J., Van de Vijver, K., Nieuwland, R., Noorden, C.J.F., Driel, W., Sturk, A., Kenter, G., Rikkert, L. and Lok, C., 2016. The histophysiology and pathophysiology of the peritoneum. Tissue and Cell 49: 95–105. 10.1016/j.tice.2016.11.004
Wang, J.-F., Xu, H.-J., He, Z.-L., Yin, Q. and Cheng, W., 2020. Crocin alleviates pain hyperalgesia in AIA rats by inhibiting the spinal Wnt5a/β-Catenin signaling pathway and glial activation. Neural Plasticity 2020: 4297483. 10.1155/2020/4297483
Wang, Y., Wang, Q., Yu, W. and Du, H., 2018. Crocin attenuates oxidative stress and myocardial infarction injury in rats. International Heart Journal 59: 387–393. 10.1536/ihj.17-114
Wei, X., Bao, Y., Zhan, X., Zhang, L., Hao, G., Zhou, J. and Chen, Q., 2019. MiR-200a ameliorates peritoneal fibrosis and functional deterioration in a rat model of peritoneal dialysis. International Urology and Nephrology 51: 889–896. 10.1007/s11255-019-02122-4
Witowski, J., Kamhieh-Milz, J., Kawka, E., Catar, R. and Jörres, A., 2018. IL-17 in peritoneal dialysis-associated inflammation and angiogenesis: conclusions and perspectives. Frontiers in Physiology 9: 1694. 10.3389/fphys.2018.01694
Wu, Z. and Hui, J., 2020. Crocin reverses 1-methyl-3-nitroso-1-nitroguanidine (MNNG)-induced malignant transformation in GES-1 cells through the Nrf2/Hippo signaling pathway. Journal of Gastrointestinal Oncology 11: 1242–1252. 10.21037/jgo-20-406
Yáñez-Mó, M., Lara-Pezzi, E., Selgas, R., Ramírez-Huesca, M., Domínguez-Jiménez, C., Jiménez-Heffernan, J.A., Aguilera, A., Sánchez-Tomero, J.A., Bajo, M.A., Álvarez, V., Castro, M.A., del Peso, G., Cirujeda, A., Gamallo, C., Sánchez-Madrid, F. and López-Cabrera, M., 2003. Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. New England Journal of Medicine 348: 403–413. 10.1056/NEJMoa020809
Zaghloul, M.S., Said, E., Suddek, G.M. and Salem, H.A., 2019. Crocin attenuates lung inflammation and pulmonary vascular dysfunction in a rat model of bleomycin-induced pulmonary fibrosis. Life Sciences 235: 116794. 10.1016/j.lfs.2019.116794
Zhao, J.-L., Guo, M.-Z., Zhu, J.-J., Zhang, T. and Min, D.-Y., 2019. Curcumin suppresses epithelial-to-mesenchymal transition of peritoneal mesothelial cells (HMrSV5) through regulation of transforming growth factor-activated kinase 1 (TAK1). Cellular & Molecular Biology Letters 24: 32. 10.1186/s11658-019-0157-x
Zhou, Y., Xu, Q., Shang, J., Lu, L. and Chen, G., 2019. Crocin inhibits the migration, invasion, and epithelial-mesenchymal transition of gastric cancer cells via miR-320/KLF5/HIF-1α signaling. Journal of Cellular Physiology 234: 17876–17885. 10.1002/jcp.28418
Asgharpour, M. and Alirezaei, A., 2021. Herbal antioxidants in dialysis patients: a review of potential mechanisms and medical implications. Renal Failure 43: 351–361. 10.1080/0886022X.2021.1880939
Chen, J., Tsim, K.W.K. and Zhao, Y.-Y., 2021. Editorial: applications of herbal medicine to control chronic kidney disease. Frontiers in Pharmacology 12: 742407. 10.3389/fphar.2021.742407
Chhimwal, J., Sharma, S., Kulurkar, P.M. and Patial, V., 2020. Crocin attenuates CCl4-induced liver fibrosis via PPAR03 mediated modulation of inflammation and fibrogenesis in rats. Human & Experimental Toxicology 39: 1639–1649. 10.1177/0960327120937048
Dariushnejad, H., Aljaf, K.A.H., Wasman, H.M., Pirzeh, L. and Ghorbanzadeh, V., 2022. Crocin inhibit the metastasis of MDA-MB-231 cell line by suppressing epithelial to mesenchymal transition through WNT/β-catenin signaling pathway. Research Square. 10.21203/rs.3.rs-1539821/v1
Duan, Z., Yao, J., Duan, N., Wang, M. and Wang, S., 2021. Sulodexide prevents peritoneal fibrosis by downregulating the expression of TGF-β1 and its signaling pathway molecules. Evidence-Based Complementary and Alternative Medicine 2021: 2052787. 10.1155/2021/2052787
Fang, K. and Gu, M., 2020. Crocin improves insulin sensitivity and ameliorates adiposity by regulating AMPK-CDK5-PPARγ signaling. BioMed Research International 2020: 9136282. 10.1155/2020/9136282
Guo, Y., Sun, L., Xiao, L., Gou, R., Fang, Y., Liang, Y., Wang, R., Li, N., Liu, F. and Tang, L., 2017. Aberrant Wnt/Beta-Catenin pathway activation in dialysate-induced peritoneal fibrosis. Frontiers in Pharmacology 8: 774–774. 10.3389/fphar.2017.00774
Guo, Y., Xiao, L., Sun, L. and Liu, F., 2012. Wnt/beta-catenin signaling: a promising new target for fibrosis diseases. Physiological Research 61: 337–346. 10.33549/physiolres.932289
Heo, J.-Y., Do, J.-Y., Lho, Y., Kim, A.Y., Kim, S.-W. and Kang, S.-H., 2021. TGF-β1 receptor inhibitor SB525334 attenuates the epithelial to mesenchymal transition of peritoneal mesothelial cells via the TGF-β1 signaling pathway. Biomedicines 9: 839. 10.3390/biomedicines9070839
Jin, W., Zhang, Y., Xue, Y., Han, X., Zhang, X., Ma, Z., Sun, S., Chu, X., Cheng, J., Guan, S., Li, Z. and Chu, L., 2020. Crocin attenuates isoprenaline-induced myocardial fibrosis by targeting TLR4/NF-κB signaling: connecting oxidative stress, inflammation, and apoptosis. Naunyn-Schmiedeberg’s Archives of Pharmacology 393: 13–23. 10.1007/s00210-019-01704-4
Kang, D.-H., 2020. Loosening of the mesothelial barrier as an early therapeutic target to preserve peritoneal function in peritoneal dialysis. Kidney Research and Clinical Practice 39: 136–144. 10.23876/j.krcp.20.052
Khan, S. and Rosner, M.H., 2018. Peritoneal dialysis for patients with end-stage renal disease and liver cirrhosis. Peritoneal Dialysis International 38: 397–401. 10.3747/pdi.2018.00008
Khatoon, E., Deka, N., Deka, M., Saikia, K.K., Baruah, M.N. and Ahmed, G.N., 2020. Clinical significance of β-catenin, hTERT, p53, and Wnt7A as biomarkers for ovarian cancer. EJGO 41: 181–187. 10.31083/j.ejgo.2020.02.5138
Kim, Y.C., Kim, K.H., Lee, S., Jo, J.-W., Park, J.Y., Park, M.-S., Tsogbadrakh, B., Lee, J.P., Lee, J.W., Kim, D.K., Oh, K.-H., Jang, I.-J., Kim, Y.S., Cha, R.-H. and Yang, S.H., 2019. ST2 blockade mitigates peritoneal fibrosis induced by TGF-β and high glucose. Journal of Cellular and Molecular Medicine 23: 6872–6884. 10.1111/jcmm.14571
Korte, M.R., Sampimon, D.E., Betjes, M.G.H. and Krediet, R.T., 2011. Encapsulating peritoneal sclerosis: the state of affairs. Nature Reviews Nephrology 7: 528–538. 10.1038/nrneph.2011.93
Liu, J., Feng, Y., Sun, C., Zhu, W., Zhang, Q.-Y., Jin, B., Shao, Q.-Y., Xia, Y.-Y., Xu, P.-F., Zhang, M. and Jiang, C.-M., 2020. Valsartan ameliorates high glucose-induced peritoneal fibrosis by blocking mTORC1 signaling. Experimental Biology and Medicine (Maywood, N.J.) 245: 983–993. 10.1177/1535370220919364
Liu, Q., Mao, H., Nie, J., Chen, W., Yang, Q., Dong, X. and Yu, X., 2008. Transforming growth factor β1 induces epithelial–mesenchymal transition by activating the Jnk–SMAD3 pathway in rat peritoneal mesothelial cells. Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 28 (Suppl 3): S88–S95. 10.1177/089686080802803s18
Rahmanian-Devin, P., Rakhshandeh, H., Baradaran Rahimi, V., Sanei-Far, Z., Hasanpour, M., Memarzia, A., Iranshahi, M. and Askari, V.R., 2021. Intraperitoneal lavage with Crocus sativus prevents postoperative-induced peritoneal adhesion in a rat model: evidence from animal and cellular studies. Oxidative Medicine and Cellular Longevity 2021: 5945101. 10.1155/2021/5945101
Ruiqi, L., Ming, P., Qihang, S., Yangyang, L., Junli, C., Wei, L., Chao, G., Xinyue, L., Kang, Y. and Hongtao, Y., 2021. Saikosaponin D inhibits peritoneal fibrosis in rats with renal failure by regulation of TGFβ1/BMP7/Gremlin1/Smad pathway. Frontiers in Pharmacology 12: 628671. 10.3389/fphar.2021.628671
Tsuzuki, T., Iwata, H., Murase, Y., Takahara, T. and Ohashi, A., 2018. Renal tumors in end-stage renal disease: a comprehensive review. International Journal of Urology 25: 780–786. 10.1111/iju.13759
Vafaei, S., Wu, X., Tu, J. and Nematollahi-Mahani, S.N., 2022. The effects of crocin on bone and cartilage diseases. Frontiers in Pharmacology 12: 830331. 10.3389/fphar.2021.830331
van baal, J., Van de Vijver, K., Nieuwland, R., Noorden, C.J.F., Driel, W., Sturk, A., Kenter, G., Rikkert, L. and Lok, C., 2016. The histophysiology and pathophysiology of the peritoneum. Tissue and Cell 49: 95–105. 10.1016/j.tice.2016.11.004
Wang, J.-F., Xu, H.-J., He, Z.-L., Yin, Q. and Cheng, W., 2020. Crocin alleviates pain hyperalgesia in AIA rats by inhibiting the spinal Wnt5a/β-Catenin signaling pathway and glial activation. Neural Plasticity 2020: 4297483. 10.1155/2020/4297483
Wang, Y., Wang, Q., Yu, W. and Du, H., 2018. Crocin attenuates oxidative stress and myocardial infarction injury in rats. International Heart Journal 59: 387–393. 10.1536/ihj.17-114
Wei, X., Bao, Y., Zhan, X., Zhang, L., Hao, G., Zhou, J. and Chen, Q., 2019. MiR-200a ameliorates peritoneal fibrosis and functional deterioration in a rat model of peritoneal dialysis. International Urology and Nephrology 51: 889–896. 10.1007/s11255-019-02122-4
Witowski, J., Kamhieh-Milz, J., Kawka, E., Catar, R. and Jörres, A., 2018. IL-17 in peritoneal dialysis-associated inflammation and angiogenesis: conclusions and perspectives. Frontiers in Physiology 9: 1694. 10.3389/fphys.2018.01694
Wu, Z. and Hui, J., 2020. Crocin reverses 1-methyl-3-nitroso-1-nitroguanidine (MNNG)-induced malignant transformation in GES-1 cells through the Nrf2/Hippo signaling pathway. Journal of Gastrointestinal Oncology 11: 1242–1252. 10.21037/jgo-20-406
Yáñez-Mó, M., Lara-Pezzi, E., Selgas, R., Ramírez-Huesca, M., Domínguez-Jiménez, C., Jiménez-Heffernan, J.A., Aguilera, A., Sánchez-Tomero, J.A., Bajo, M.A., Álvarez, V., Castro, M.A., del Peso, G., Cirujeda, A., Gamallo, C., Sánchez-Madrid, F. and López-Cabrera, M., 2003. Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. New England Journal of Medicine 348: 403–413. 10.1056/NEJMoa020809
Zaghloul, M.S., Said, E., Suddek, G.M. and Salem, H.A., 2019. Crocin attenuates lung inflammation and pulmonary vascular dysfunction in a rat model of bleomycin-induced pulmonary fibrosis. Life Sciences 235: 116794. 10.1016/j.lfs.2019.116794
Zhao, J.-L., Guo, M.-Z., Zhu, J.-J., Zhang, T. and Min, D.-Y., 2019. Curcumin suppresses epithelial-to-mesenchymal transition of peritoneal mesothelial cells (HMrSV5) through regulation of transforming growth factor-activated kinase 1 (TAK1). Cellular & Molecular Biology Letters 24: 32. 10.1186/s11658-019-0157-x
Zhou, Y., Xu, Q., Shang, J., Lu, L. and Chen, G., 2019. Crocin inhibits the migration, invasion, and epithelial-mesenchymal transition of gastric cancer cells via miR-320/KLF5/HIF-1α signaling. Journal of Cellular Physiology 234: 17876–17885. 10.1002/jcp.28418
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