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Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1

  • Authors:
    • Xiaoshu Pu
    • Xiaolei Cao
    • Hongyan Liu
    • Wenlian Huang
    • Lanfang Zhang
    • Ting Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Burn and Plastic Surgery, Nanchong Central Hospital, Nanchong, Sichuan 637000, P.R. China, General Surgery Department, The People's Hospital of Shunqing District, Nanchong Central Hospital, Nanchong, Sichuan 637000, P.R. China, Department of Burn and Plastic Surgery, Nanchong Central Hospital, Nanchong, Sichuan 637000, P.R. China, Department of Critical Care Medicine, Nanchong Central Hospital, Nanchong, Sichuan 637000, P.R. China
    Copyright: © Pu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 310
    |
    Published online on: May 11, 2023
       https://doi.org/10.3892/etm.2023.12009
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Abstract

Isorhamnetin (IH) is a type of flavonoid with multiple biological activities, including cardioprotective, antitumor, anti‑inflammatory and antioxidant activities. However, the role and potential mechanism of IH in keloids are still not completely understood. The aim of the present study was to explore how IH affects keloid progression. In the present study, cell proliferation was evaluated using the Cell Counting Kit‑8 assay and immunofluorescence. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. The expression levels of fibrosis‑related proteins were measured using western blot analysis and immunofluorescence. In addition, the binding between IH and sphingosine‑1‑phosphate receptor‑1 (S1PR1) was analyzed using the TargetNet database, and molecular docking was performed using Zinc, PubChem, AutoDockTools 1.5.6 and Discovery Studio 4.5 software. The expression levels of proteins in the PI3K/AKT pathway were detected by western blot analysis. The results showed that IH inhibited the proliferation, invasion, migration and fibrosis of keloid fibroblasts. The binding of IH and S1PR1 was verified and molecular docking was performed. Notably, IH significantly suppressed the expression levels of S1PR1, phosphorylated (p)‑PI3K and p‑AKT. Furthermore, the silencing of S1PR1 suppressed the cell proliferation, migration, invasion and fibrosis of keloid fibroblasts, as well as the expression of the PI3K/AKT pathway proteins. Conversely, S1PR1 upregulation reversed the inhibitory effects of IH on keloid fibroblast proliferation, migration, invasion and fibrosis. In conclusion, the results revealed that IH suppressed the proliferation, migration, invasion and fibrosis of keloid fibroblasts by targeting the S1PR1/PI3K/AKT pathway, suggesting that IH may be a promising drug for the treatment of keloids.
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1 

Unahabhokha T, Sucontphunt A, Nimmannit U, Chanvorachote P, Yongsanguanchai N and Pongrakhananon V: Molecular signalings in keloid disease and current therapeutic approaches from natural based compounds. Pharm Biol. 53:457–463. 2015.PubMed/NCBI View Article : Google Scholar

2 

Hawash AA, Ingrasci G, Nouri K and Yosipovitch G: Pruritus in keloid scars: Mechanisms and treatments. Acta Derm Venereol. 101(adv00582)2021.PubMed/NCBI View Article : Google Scholar

3 

Mofikoya BO, Adeyemo WL and Abdus-salam AA: Keloid and hypertrophic scars: A review of recent developments in pathogenesis and management. Nig Q J Hosp Med. 17:134–139. 2007.PubMed/NCBI View Article : Google Scholar

4 

Ogawa R: Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci. 18(606)2017.PubMed/NCBI View Article : Google Scholar

5 

Qiao XF and Li X: Comparative study of surgical treatment combined with various methods for treatment of ear scar. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 31:1341–1343. 2017.PubMed/NCBI View Article : Google Scholar : (In Chinese).

6 

Love PB and Kundu RV: Keloids: An update on medical and surgical treatments. J Drugs Dermatol. 12:403–409. 2013.PubMed/NCBI

7 

Lee HJ and Jang YJ: Recent understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids. Int J Mol Sci. 19(711)2018.PubMed/NCBI View Article : Google Scholar

8 

Wang Q, Wang P, Qin Z, Yang X, Pan B, Nie F and Bi H: Altered glucose metabolism and cell function in keloid fibroblasts under hypoxia. Redox Biol. 38(101815)2021.PubMed/NCBI View Article : Google Scholar

9 

Zhou P, Shi L, Li Q and Lu D: Overexpression of RACK1 inhibits collagen synthesis in keloid fibroblasts via inhibition of transforming growth factor-β1/Smad signaling pathway. Int J Clin Exp Med. 8:15262–15268. 2015.PubMed/NCBI

10 

Rodríguez L, Badimon L, Méndez D, Padró T, Vilahur G, Peña E, Carrasco B, Vogel H, Palomo I and Fuentes E: Antiplatelet Activity of Isorhamnetin via Mitochondrial Regulation. Antioxidants (Basel). 10(666)2021.PubMed/NCBI View Article : Google Scholar

11 

Gong G, Guan YY, Zhang ZL, Rahman K, Wang SJ, Zhou S, Luan X and Zhang H: Isorhamnetin: A review of pharmacological effects. Biomed Pharmacother. 128(110301)2020.PubMed/NCBI View Article : Google Scholar

12 

Luo W, Liu Q, Jiang N, Li M and Shi L: Isorhamnetin inhibited migration and invasion via suppression of Akt/ERK-mediated epithelial-to-mesenchymal transition (EMT) in A549 human non-small-cell lung cancer cells. Bioscience Reports. 39:2019.PubMed/NCBI View Article : Google Scholar

13 

Zheng Q, Tong M, Ou B, Liu C, Hu C and Yang Y: Isorhamnetin protects against bleomycin-induced pulmonary fibrosis by inhibiting endoplasmic reticulum stress and epithelial-mesenchymal transition. Int J Mol Med. 43:117–126. 2019.PubMed/NCBI View Article : Google Scholar

14 

Yang JH, Kim SC, Kim KM, Jang CH, Cho SS, Kim SJ, Ku SK, Cho IJ and Ki SH: Isorhamnetin attenuates liver fibrosis by inhibiting TGF-β/Smad signaling and relieving oxidative stress. Eur J Pharmacol. 783:92–102. 2016.PubMed/NCBI View Article : Google Scholar

15 

Lee JY, Yang CC, Chao SC and Wong TW: Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathol. 26:379–384. 2004.PubMed/NCBI View Article : Google Scholar

16 

Elsaie ML: Update on management of keloid and hypertrophic scars: A systemic review. J Cosmet Dermatol. 20:2729–2738. 2021.PubMed/NCBI View Article : Google Scholar

17 

Lim KH, Itinteang T, Davis PF and Tan ST: Stem cells in keloid lesions: A review. Plast Reconstr Surg Glob Open. 7(e2228)2019.PubMed/NCBI View Article : Google Scholar

18 

Li J, Xu Y, Lin Z, Guan L, Chen S and Zhou L: Isorhamnetin inhibits amplification of influenza A H1N1 virus inflammation mediated by interferon via the RIG-I/JNK pathway. Ann Transl Med. 9(1327)2021.PubMed/NCBI View Article : Google Scholar

19 

Ren X, Han L, Li Y, Zhao H, Zhang Z, Zhuang Y, Zhong M, Wang Q, Ma W and Wang Y: Isorhamnetin attenuates TNF-α-induced inflammation, proliferation, and migration in human bronchial epithelial cells via MAPK and NF-κB pathways. Anat Rec (Hoboken). 304:901–913. 2021.PubMed/NCBI View Article : Google Scholar

20 

Hu J, Zhang Y, Jiang X, Zhang H, Gao Z, Li Y, Fu R, Li L, Li J, Cui H and Gao N: ROS-mediated activation and mitochondrial translocation of CaMKII contributes to Drp1-dependent mitochondrial fission and apoptosis in triple-negative breast cancer cells by isorhamnetin and chloroquine. J Exp Clin Cancer Res. 38(225)2019.PubMed/NCBI View Article : Google Scholar

21 

Ganbold M, Owada Y, Ozawa Y, Shimamoto Y, Ferdousi F, Tominaga K, Zheng YW, Ohkohchi N and Isoda H: Isorhamnetin alleviates steatosis and fibrosis in mice with nonalcoholic steatohepatitis. Sci Rep. 9(16210)2019.PubMed/NCBI View Article : Google Scholar

22 

Liu N, Feng J, Lu X, Yao Z, Liu Q, Lv Y, Han Y, Deng J and Zhou Y: Isorhamnetin Inhibits liver fibrosis by reducing autophagy and inhibiting extracellular matrix formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK pathways. Mediators Inflamm. 2019(6175091)2019.PubMed/NCBI View Article : Google Scholar

23 

Zhai T, Zhang X, Hei Z, Jin L, Han C, Ko AT, Yu X and Wang J: Isorhamnetin inhibits human gallbladder cancer cell proliferation and metastasis via PI3K/AKT signaling pathway inactivation. Front Pharmacol. 12(628621)2021.PubMed/NCBI View Article : Google Scholar

24 

Cartier A and Hla T: Sphingosine 1-phosphate: Lipid signaling in pathology and therapy. Science. 366(eaar5551)2019.PubMed/NCBI View Article : Google Scholar

25 

Anu B, Namitha NN and Harikumar KB: S1PR1 signaling in cancer: A current perspective. Adv Protein Chem Struct Biol. 125:259–274. 2021.PubMed/NCBI View Article : Google Scholar

26 

Donati C, Cencetti F, Bernacchioni C, Vannuzzi V and Bruni P: Role of sphingosine 1-phosphate signalling in tissue fibrosis. Cell Signal. 78(109861)2021.PubMed/NCBI View Article : Google Scholar

27 

Jung SH, Song YK, Chung H, Ko HM, Lee SH, Jo DI, Kim B, Lee DH and Kim SH: Association between sphingosine-1-phosphate-induced signal transduction via mitogen-activated protein kinase pathways and keloid formation. Arch Dermatol Res. 311:711–719. 2019.PubMed/NCBI View Article : Google Scholar

28 

Tu T, Huang J, Lin M, Gao Z, Wu X, Zhang W, Zhou G, Wang W and Liu W: CUDC-907 reverses pathological phenotype of keloid fibroblasts in vitro and in vivo via dual inhibition of PI3K/Akt/mTOR signaling and HDAC2. Int J Mol Med. 44:1789–1800. 2019.PubMed/NCBI View Article : Google Scholar

29 

Xin Y, Min P, Xu H, Zhang Z and Zhang Y and Zhang Y: CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway. Burns Trauma. 8(tkaa025)2020.PubMed/NCBI View Article : Google Scholar

30 

Liu X, Wu J, Zhu C, Liu J, Chen X, Zhuang T, Kuang Y, Wang Y, Hu H, Yu P, et al: Endothelial S1pr1 regulates pressure overload-induced cardiac remodelling through AKT-eNOS pathway. J Cell Mol Med. 24:2013–2026. 2020.PubMed/NCBI View Article : Google Scholar

31 

Rostami N, Nikkhoo A, Ajjoolabady A, Azizi G, Hojjat-Farsangi M, Ghalamfarsa G, Yousefi B, Yousefi M and Jadidi-Niaragh F: S1PR1 as a novel promising therapeutic target in cancer therapy. Mol Diagn Ther. 23:467–487. 2019.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Pu X, Cao X, Liu H, Huang W, Zhang L and Jiang T: Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1. Exp Ther Med 26: 310, 2023.
APA
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., & Jiang, T. (2023). Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1. Experimental and Therapeutic Medicine, 26, 310. https://doi.org/10.3892/etm.2023.12009
MLA
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., Jiang, T."Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1". Experimental and Therapeutic Medicine 26.1 (2023): 310.
Chicago
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., Jiang, T."Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1". Experimental and Therapeutic Medicine 26, no. 1 (2023): 310. https://doi.org/10.3892/etm.2023.12009
Copy and paste a formatted citation
x
Spandidos Publications style
Pu X, Cao X, Liu H, Huang W, Zhang L and Jiang T: Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1. Exp Ther Med 26: 310, 2023.
APA
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., & Jiang, T. (2023). Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1. Experimental and Therapeutic Medicine, 26, 310. https://doi.org/10.3892/etm.2023.12009
MLA
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., Jiang, T."Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1". Experimental and Therapeutic Medicine 26.1 (2023): 310.
Chicago
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., Jiang, T."Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1". Experimental and Therapeutic Medicine 26, no. 1 (2023): 310. https://doi.org/10.3892/etm.2023.12009
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