Recombinant human interferon alpha-2b inhibits the proliferation and migration of scar fibroblasts

doi:10.12307/2022.846

Abstract

Abstract: BACKGROUND: Recombinant human interferon α-2b is a cytokine with antiviral, antiproliferative, antitumor, and immunomodulatory activities, which has certain preventive and curative effects on scar tissue.
OBJECTIVE: To explore the effects of recombinant human interferon α-2b on scar fibroblasts and to observe its effects on the proliferation and migration abilities of scar fibroblasts.
METHODS: In vitro scar fibroblasts were cultured to logarithmic growth phase and treated with 0, 5 000, 10 000, 20 000 IU/mL recombinant human interferon α-2b for 48 hours. Cell proliferation was observed by EdU staining and cell migration was detected through cell scratch test and Transwell test. Expression levels of proliferating cell nuclear antigen and matrix metalloproteinase 2, proliferation- and migration-associated proteins of scar fibroblasts were detected by western blot assay.
RESULTS AND CONCLUSION: The results of in vitro cell experiments showed that, compared with the control group, recombinant human interferon α-2b could significantly decrease the number of EdU-positive cells, the wound healing rate, the number of migrated cells, and the protein levels of proliferating cell nuclear antigen and matrix metalloproteinase 2 (P < 0.05). All these findings indicate that recombinant human interferon α-2b can inhibit the proliferation and migration of scar fibroblasts.

Key words: recombinant human interferon α-2b, hypertrophic scar, fibroblast, cell migration

CLC Number:

Wang Rui, Yu Fei, Liu Taibin, Hou Xiuli, Liu Zhendong, Huo Jing, Song Jianbo. Recombinant human interferon alpha-2b inhibits the proliferation and migration of scar fibroblasts[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(29): 4611-4615.

Figures/Tables 4

References

[1] YANG SW, GENG ZJ, MA K, et al. Comparison ofthe histological morphology between normal skin and scar tissue. J Huazhong Univ Sci Technolog Med Sci. 2016;36(2):265-269.
[2] FINNERTY CC, JESCHKE MG, BRANSKI LK, et al. Hypertrophic scarring: the greatest unmet challenge after burn injury. Lancet. 2016;388 (10052):1427-1436.
[3] KIM JY, WILLARD JJ, SUPP DM, et al. Burn Scar Biomechanics after Pressure Garment Therapy. Plast Reconstr Surg. 2015;136(3):572-558.
[4] KAFKA M,COLLINS V,KAMOLZ LP, et al. Evidence of invasive and noninvasive treatment modalities for hypertrophic scars: A systematic review. Wound Repair Regen.2017;25(1):139-144.
[5] LEWCZUK N, ZDEBIK A, BOGUSŁAWSKA J. Interferon Alpha 2a and 2b in Ophthalmology: A Review. J Interferon Cytokine Res. 2019;39(5):259-272.
[6] BERMAN B, DUNCAN MR. Short-term keloid treatment in vivo with human interferon alfa-2b results in a selective and persistent normalization of keloidal fibroblast collagen, glycosaminoglycan, and collagenase production in vitro. J Am Acad Dermatol. 1989;21:694-702.
[7] GONG YF, ZHANG XM, LIU F, et al. Inhibitory effect of recombinant human endostatin on the proliferation of hypertrophic scar fibroblasts in a rabbit ear model. Eur J Pharmacol. 2016;791:647-654.
[8] YIN MY, LI H, ZHANG YN, et al. Interferon Alpha-2b eye drops prevent recurrence of pterygium after the bare sclera technique: a single-center, sequential, and controlled study. Cornea. 2019;38(10):1239-1244.
[9] CORNELISSEN AM, VONDEN HOFF IW, MALTHA JC, et al. Effects of interferons on proliferation and collagen synthesis of rat palatal wound fibroblasts. Arch Oral Biol. 1999;44(7):541-547.
[10] 黄勇,邢新,李军辉,等.干扰素α-2b对瘢痕疙瘩成纤维细胞增殖及端粒酶活性的影响[J]. 第二军医大学学报,2006,27(12):1384-1386.
[11] 孔亚男,陆宏,陈颖,等. 青光眼滤过术后瘢痕形成机制及抗瘢痕化研究进展[J]. 国际眼科杂志,2019,19(10):1688-1691.
[12] JIN Q, GUI L, NIU F, et al. Macrophages in keloid are potent at promoting the differentiation and function of regulatory T cells. Exp Cell Res. 2018; 362(2):472-476.
[13] VERMA SK, GARIKIPATI VNS, KRISHNAMURTHY P, et al. Interleukin-10 inhibits bone marrow fibroblast progenitor cell-mediated cardiac fibrosis in pressure-overloaded myocardium. Circulation. 2017;136(10): 940-953.
[14] OGAWA R. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int J Mol Sci. 2017;18(3):E606.
[15] GONG YF, ZHANG XM, LIU F, et al. Inhibitory effect of recombinant human endostatin on the proliferation of hypertrophic scar fibroblasts in a rabbit ear model. Eur J Pharmacol. 2016;791:647-654.
[16] YAN L, WANG LZ, XIAO R, et al. Inhibition of microRNA-21-5p reduces keloid fibroblast autophagy and migration by targeting PTEN after electron beam irradiation. Lab Invest. 2020;100(3):387-399.
[17] LUO L, LI J, LIU H, et al. Adiponectin Is Involved in Connective Tissue Growth Factor-Induced Proliferation, Migration and Overproduction of the Extracellular Matrix in Keloid Fibroblasts. Int J Mol Sci. 2017;18(5):1044.
[18] WITT E, MALIRI A, MCGROUTHER DA, et al. RAC activity in keloid disease: comparative analysis of fibroblasts from margin of keloid to its surrounding normal skin. Eplasty. 2008;8:e19.
[19] BANDURSKA K, KRÓL I, MYGA-NOWAK M. Interferons: between structure and function]. Postepy Hig Med Dosw (Online). 2014;68:428-440.
[20] ASMANA NR. Human Interferon Alpha-2b: A Therapeutic Protein for Cancer Treatment. Scientifica. 2014:970315.
[21] HU JH, CHANG ML, HUANG TJ, et al. Comparison of Compliance and Efficacy of Pegylated Interferon α-2a and α-2b in Adults with Chronic Hepatitis C. J Interferon Cytokine Res. 2019;39(4):205-213.
[22] NINGRUM RA. Human interferon alpha-2b: a therapeutic protein for cancer treatment. Scientifica (Cairo). 2014;970315:1-8.
[23] KATLA S, YOGANAND KNR, HINGANE S, et al. Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach. Enzyme Microb Technol. 2019;128:49-58.
[24] 刘振东,王瑞,李小磊,王静成. 干扰素α-2b 抑制瘢痕形成的研究与热点[J]. 中国组织工程研究,2021,25(2):159-163.
[25] TSAI WC, CHENG JW, CHEN JL, et al. Low-level laser irradiation stimulates tenocyte proliferation in association with increased NO synthesis and upregulation of PCNA and cyclins. Lasers Med Sci. 2014; 29(4):1377-1384.
[26] ORGAZ JL, PANDYA P, DALMEIDA R, et al. Diverse matrix metalloproteinase functions regulate cancer amoeboid migration. Nat Commun. 2014;5: 4255.
[27] CHO YR, KIM JH, KIM JK, et al. Broussonetia kazinoki modulates the expression of VEGFR-2 and MMP-2 through the inhibition of ERK, Akt and p70S6Kdependent signaling pathways: Its implication in endothelial cell proliferation, migration and tubular formation. Oncol Rep. 2014; 32(4):1531-1536.
[28] YIJING L, LIU H, YUAN C, et al. The effects of qindan-capsule-containing serum on the TGF-β1/ERK signaling pathway, matrix metalloproteinase synthesis and cell function in adventitial fibroblasts. Pharm Biol. 2013; 51(6):712-721.
[29] HAM SA, LEE H, HWANG JS, et al. Activation of peroxisome proliferator-activated receptor δ inhibits angiotensin II-induced activation of matrix metalloproteinase-2 in vascular smooth muscle cells. J Vasc Res. 2014; 51(3):221-230.
[30] FAN X, WANG E, WANG X, et al. MicroRNA-21 is a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs. Exp Mol Pathol. 2014;96(2):242-249.
[31] 徐志山,回蔷,李伟,等. miR-194-3p对瘢痕疙瘩成纤维细胞迁移的作用[J]. 中华整形外科杂志,2018,34(11):964-970.
[32] LICHTMAN MK, OTERO-VINAS M, FALANGA V. Transforming growth factor beta (TGF-β) isoforms in wound healing and fibrosis. Wound Repair Regen. 2016;24(2):215-222.
[33] Berman B, Maderal A, Raphael B. Keloids and Hypertrophic Scars: Pathophysiology, Classification, and Treatment. Dermatol Surg. 2017;43: S3-S18.
[34] LODYGA M, HINZ B. TGF-β1 - A truly transforming growth factor in fibrosis and immunity. Semin Cell Dev Biol. 2020;101:123-139.