Regulatory Role of PI3K/Akt Signaling Pathway in Hypertrophic Scar

Weimin LIU; Yiqun MA; Zhuo TIAN; Yang TANG

doi:10.12259/j.issn.2095-610X.S20230313

Volume 44 Issue 3

Mar. 2023

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Weimin LIU, Yiqun MA, Zhuo TIAN, Yang TANG. Regulatory Role of PI3K/Akt Signaling Pathway in Hypertrophic Scar[J]. Journal of Kunming Medical University, 2023, 44(3): 22-27. doi: 10.12259/j.issn.2095-610X.S20230313

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Weimin LIU, Yiqun MA, Zhuo TIAN, Yang TANG. Regulatory Role of PI3K/Akt Signaling Pathway in Hypertrophic Scar[J]. Journal of Kunming Medical University, 2023, 44(3): 22-27. doi: 10.12259/j.issn.2095-610X.S20230313

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Regulatory Role of PI3K/Akt Signaling Pathway in Hypertrophic Scar

doi: 10.12259/j.issn.2095-610X.S20230313

1.
Dept. of Dermatological，Affiliated Hospital of Yunnan University，The Second People’s Hospital of Yunnan Province，Kunming Yunnan 560021
2.
Dept. of Burn Trauma Plastic Surgery，Children's Hospital Affiliated to Kunming Medical University，Kunming Yunnan 650228
3.
Dept. of Dermatological，The Affiliated Nanyang Central Hospital of Zhengzhou University，Zhengzhou Henan 473000
4.
Dept. of Dermatological，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Received Date: 2022-10-18
Available Online: 2023-03-02
Publish Date: 2023-03-25

Abstract

Abstract

Objective To explore the regulatory role of PI3K/Akt signaling pathway in the hypertrophic scar. Methods The rabbit ear hypertrophic scar model was established and randomly divided into four groups, including normal rabbit ear skin group （A）, hypertrophic scar model group （B）, DMSO-stimulated hypertrophic scar model group （C）, and PI3K-specific inhibitor （LY294002） stimulated model group （D）. Morphological changes of rabbit ear scar were observed by histopathology. The expression of phosphorylation of Akt[S473] and Akt[T308] was examined by immunohistochemistry and western blot. Immunofluorescence double staining was performed to assess the co-localization of p-Akt[S473] and p-Akt[T308]. The TUNEL assay was used to detect the fibroblasts’ apoptosis in skin tissues. Results Scar thickness and fibroblast count were significantly higher in the D group than that in the B and C groups, but the difference was not statistically significant between the B group and the C group. The results of immunohistochemistry and western blot assay confirmed that the expression of p-Akt[T308] and p-Akt[S473] were significantly higher in the B group than in the A group, but significantly lower in the D group than in the C group. The expression of p-Akt[T308] and p-Akt[S473] was significantly enhanced in the B group compared with the C group. Immunofluorescence double staining showed that p-Akt[T308] and p-Akt[S473] were mainly co-localized in the cytoplasm in scar tissue, and their co-expression was lower in the D group than in the B group. TUNEL assay results confirmed that the apoptosis level of fibroblast was significantly downregulated in skin tissue in the B group compared with the A group, and the apoptosis level of fibroblast was higher in the D group than in the C （P < 0.01）. Conclusion Blocking the PI3K/Akt signaling pathway can accelerate fibroblast apoptosis by inhibiting Akt phosphorylation, and then alleviate hypertrophic scar formation.
- Hypertrophic scar,
- LY294002,
- Phosphatidylinositol 3-kinase,
- Apoptosis

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References(15)

References

[1]	Ogawa R,Dohi T,Tosa M,et al. The latest strategy for keloid and hypertrophic scar prevention and treatment: The nippon medical school (NMS) protocol[J]. J Nippon Med Sch,2021,88(1):2-9. doi: 10.1272/jnms.JNMS.2021_88-106
[2]	Raktoe R S,van Haasterecht L,Antonovaite N,et al. The effect of TGFβRI inhibition on extracellular matrix structure and stiffness in hypertrophic scar-specific fibroblast-derived matrix models[J]. Biochem Biophys Res Commun,2021,559(6):245-251.
[3]	Mercurio L,Albanesi C,Madonna S. Recent updates on the involvement of PI3K/AKT/mTOR molecular cascade in the pathogenesis of hyperproliferative skin disorders[J]. Front Med (Lausanne),2021,8(4):665647.
[4]	Liu C,Chen K,Wang H,et al. Gastrin attenuates renal ischemia/reperfusion injury by a PI3K/Akt/bad-mediated anti-apoptosis signaling[J]. Front Pharmacol,2020,11(11):540479.
[5]	He T,Zhang Y,Liu Y,et al. MicroRNA-494 targets PTEN and suppresses PI3K/AKT pathway to alleviate hypertrophic scar formation[J]. J Mol Histol,2019,50(4):315-323. doi: 10.1007/s10735-019-09828-w
[6]	Tu T,Huang J,Lin M,et al. CUDC-907 reverses pathological phenotype of keloid fibroblasts in vitro and in vivo via dual inhibition of PI3K/Akt/mTOR signaling and HDAC2[J]. Int J Mol Med,2019,44(5):1789-1800.
[7]	Md Mokhtar A H,Malik I A,Abd Aziz N A A,et al. LY294002,a PI3K pathway inhibitor,prevents leptin-induced adverse effects on spermatozoa in sprague-dawley rats[J]. Andrologia,2019,51(3):e13196. doi: 10.1111/and.13196
[8]	Long H Y,Wang C Y,Yang Y E. LY294002,a PI3K inhibitor,attenuates Tourette syndrome in rats[J]. Metab Brain Dis,2017,32(5):1619-1625. doi: 10.1007/s11011-017-0051-z
[9]	Luo L,Li J,Wu Y,et al. Adiponectin,but Not TGF-β1,CTGF,IL-6 or TNF-α,may be a potential anti-inflammation and anti-fibrosis factor in keloid[J]. J Inflamm Res,2021,14(3):907-916.
[10]	Wu X,Pu L,Chen W,et al. LY294002 attenuates inflammatory response in endotoxin-induced uveitis by downregulating JAK3 and inactivating the PI3K/Akt signaling[J]. Immunopharmacol Immunotoxicol,2022,44(4):510-518. doi: 10.1080/08923973.2022.2055565
[11]	Chen H,Xu K,Sun C,et al. Inhibition of ANGPT2 activates autophagy during hypertrophic scar formation via PI3K/AKT/mTOR pathway[J]. An Bras Dermatol,2022,98(1):26-35.
[12]	Ma F, Shen J, Zhang H, et al. A novel lncRNA FPASL regulates fibroblast proliferation via the PI3K/AKT and MAPK signaling pathways in hypertrophic scar[J]. Acta Biochim Biophys Sin （Shanghai）, 2022. http://doi.org/10.3724/abbs.2022122. [Online ahead of print].
[13]	Zhi Y, Wang H, Huang B, et al. Panax Notoginseng Saponins suppresses TRPM7 via the PI3K/AKT pathway to inhibit hypertrophic scar formation in vitro. Burns, 2021, 47（4）: 894-905.
[14]	Shi W,Wu Y,Bian D. p75NTR silencing inhibits proliferation,migration,and extracellular matrix deposition of hypertrophic scar fibroblasts by activating autophagy through inhibiting the PI3K/Akt/mTOR pathway[J]. Can J Physiol Pharmacol,2021,99(4):349-359. doi: 10.1139/cjpp-2020-0219
[15]	Wu X,Wang Z,Wu G,et al. Tetramethylpyrazine induces apoptosis and inhibits proliferation of hypertrophic scar-derived fibroblasts via inhibiting the phosphorylation of AKT[J]. Front Pharmacol,2020,11(5):602.

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