Research on the mechanism of POSTEN promoting keloid formation via endoplasmic reticulum stress and proliferation

doi:10.13418/j.issn.1001-165x.2026.3.10

PDF(3669 KB)

Chinese Journal of Clinical Anatomy ›› 2026, Vol. 44 ›› Issue (3) : 311-316. DOI: 10.13418/j.issn.1001-165x.2026.3.10

Research on the mechanism of POSTEN promoting keloid formation via endoplasmic reticulum stress and proliferation

Wang Guohe, Feng Peng*, Zhang Yue, Li Ziyin, Du Aoyu

Author information +

History +

Abstract

Objective To reveal the mechanism of periostin (POSTEN) in the formation of keloids and its influence on the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling pathway, endoplasmic reticulum stress (ER Stress) regulation, and cell proliferation behavior. Methods Venn analysis and STRING/Cytoscape protein interaction network construction were performed using the GSE44270 dataset and Genecards database. Western blot and qRT-PCR were used to detect POSTEN expression. Immunofluorescence was used for localization. Transwell and EdU assays were used to evaluate migration and proliferation. Western blot was used to detect the levels of key proteins in the NFκB pathway (p-NFκB) and endoplasmic reticulum stress markers (GRP78, CHOP). Results Compared with normal human dermal fibroblasts (NF), the expression levels of POSTEN protein and mRNA in human keloid fibroblasts (KF) were significantly increased (P<0.05). After POSTEN knockdown, POSTEN expression was significantly decreased (P<0.05), accompanied by a significant reduction in EdU positive cell rate and the number of migrating and invasive cells (P<0.05), and the levels of p-NFκB, GRP78, and CHOP proteins were also significantly decreased (P<0.05). Conclusions POSTEN is highly expressed in keloid fibroblasts. It can induce endoplasmic reticulum stress by activating the NFκB signaling pathway, thereby promoting the proliferation, migration and invasion of keloid fibroblasts, and ultimately facilitating the formation of keloids; Targeted inhibition of POSTEN may become a potential strategy for the treatment of keloids.

Key words

Keloid / / / POSTEN / / / Proliferation / / / Endoplasmic reticulum stress / / / NFκB

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

Wang Guohe, Feng Peng, Zhang Yue, Li Ziyin, Du Aoyu. Research on the mechanism of POSTEN promoting keloid formation via endoplasmic reticulum stress and proliferation[J]. Chinese Journal of Clinical Anatomy. 2026, 44(3): 311-316 https://doi.org/10.13418/j.issn.1001-165x.2026.3.10

References

[1] Naik PP. Novel targets and therapies for keloid[J]. Clin Exp Dermatol, 2022, 47(3): 507-515. DOI:10.1111/ced.14920.
[2] Li CY, Xie RX, Zhang SW, et al. Metabolism, fibrosis, and apoptosis: The effect of lipids and their derivatives on keloid formation[J]. Int Wound J, 2024, 21(2):e14733-147734. DOI:10.1111/iwj.14733.
[3] Hawash AA, Ingrasci G, Nouri K, et al. Pruritus in keloid scars: mechanisms and treatments[J]. Acta Derm Venereol, 2021, 101(10):adv00582-00583. DOI:10.2340/00015555-3923.
[4] Ud-Din S, Bayat A. Keloid scarring or disease: Unresolved quasi-neoplastic tendencies in the human skin[J]. Wound Repair Regen, 2020, 28(3):422-426. DOI:10.1111/wrr.
[5] Kim S, Lee SE, Yi S, et al. Tauroursodeoxycholic acid decreases keloid formation by reducing endoplasmic reticulum stress as implicated in the pathogenesis of keloid[J]. Int J Mol Sci, 2021, 22(19):10765-10766. DOI:10.3390/ijms221910765.
[6] Shi M, Zhang L, Bi F, et al. ALKBH5 inhibits YTHDF2-m6A-Mediated degradation of RCN1 mRNA to promote keloid formation by activating IRE1α-XBP1-mediated ER stress[J]. J Cosmet Dermatol, 2025, 24(4):e70177-70178. DOI:10.1111/jocd.70177.
[7] Piao M, Feng G. The deubiquitinating enzyme USP37 promotes keloid fibroblasts proliferation and collagen production by regulating the c-Myc expression[J]. Int Wound J, 2023, 20(5):1517-1524. DOI:10.1111/iwj.
[8] Hong YK, Wu CH, Lin YC, et al. ASC-J9 blocks cell proliferation and extracellular matrix production of keloid fibroblasts through inhibiting STAT3 signaling[J]. Int J Mol Sci, 2022, 23(10):5549-5550. DOI:10.3390/ijms23105549.
[9] Katayama Y, Naitoh M, Kubota H, et al. Chondroitin sulfate promotes the proliferation of keloid fibroblasts through activation of the integrin and protein kinase B pathways[J]. Int J Mol Sci, 2020, 21(6):1955-1956. DOI:10.3390/ijms21061955.
[10]Zhu G, Cai J, Zhang J, et al. Abnormal nuclear factor (NF)-kappaB signal pathway and aspirin inhibits tumor necrosis factor alpha-induced NF-kappaB activation in keloid fibroblasts[J]. Dermatol Surg, 2007, 33(6): 697-708. DOI:10.1111/j.1524-4725.2007.33146.x.
[11]Wang Z, Zhu D, Yang F, et al. POSTN knockdown suppresses IL-1β-induced inflammation and apoptosis of nucleus pulposus cells via inhibiting the NF-κB pathway and alleviates intervertebral disc degeneration[J]. J Cell Commun Signal, 2024, 18(2): e12030-12031. DOI:10.1002/ccs3.12030.
[12]Xu H, Wang Z, Yang H, et al. Bioinformatics analysis and identification of dysregulated POSTN in the pathogenesis of keloid[J]. Int Wound J, 2023, 20(5):1700-1711. DOI:10.1111/iwj.14031.
[13]Tian J, Liu X, Zhu D, et al. Periostin regulates the activity of keloid fibroblasts by activating the JAK/STAT signaling pathway[J]. Heliyon, 2024,10(21):e38821-35522. DOI:10.1016/j.heliyon.2024.e38821.
[14]邱韵洁, 吴义珠, 石志伟, 等. 肌细胞增强因子2C 通过促进叉头框蛋白O1 转录对瘢痕疙瘩成纤维细胞生物学功能的影响 [J].临床皮肤科杂志, 2025, 54（8）: 467-475. DOI:10.16761/j.cnki.1000-4963.2025. 08.005.
Qiu YJ, Wu YZ, Shi ZW, et al. Effect of MEF2C on the biological functions of keloid fibroblasts through promoting FOXO1transcription[J]. Journal of Clinical Dermatology, 2025, 54(8): 467-475. DOI: 10.1016/j.pbiomolbio.2017.02.002.
[15]Wang ZC, Zhao WY, Cao Y, et al. The roles of inflammation in keloid and hypertrophic scars[J]. Front Immunol, 2020, 11:603187-603188. DOI:10.3389/fimmu.2020.603187.
[16]Kim HJ, Kim YH. Comprehensive insights into keloid pathogenesis and advanced therapeutic strategies[J]. Int J Mol Sci, 2024, 25(16):8776-8777. DOI:10.3390/ijms25168776.
[17]Macarak EJ, Wermuth PJ, Rosenbloom J, et al. Keloid disorder: Fibroblast differentiation and gene expression profile in fibrotic skin diseases[J]. Exp Dermatol, 2021, 30(1):132-145.DOI:10.1111/exd. 14243.
[18]Chen L, Su Y, Yin B, et al. LARP6 regulates keloid fibroblast proliferation, invasion, and ability to synthesize collagen[J]. J Invest Dermatol, 2022 , 142(9):2395-2405. DOI:10.1016/j.jid.2022.01.028.
[19]Walsh LA, Wu E, Pontes D, et al. Keloid treatments: an evidence-based systematic review of recent advances[J]. Syst Rev, 2023,12(1):42-43. DOI:10.1186/s13643-023-02192-7.
[20]Tai Y, Zheng L, Liao J, et al. Roles of the HIF-1α pathway in the development and progression of keloids[J]. Heliyon, 2023, 9(8):e18651-18652. DOI:10.1016/j.heliyon.2023.e18651.
[21]Hernández-Bule ML, Toledano-Macías E, Pérez-González LA, et al. Anti-fibrotic effects of RF electric currents[J]. Int J Mol Sci, 2023, 24(13):10986-10987. DOI:10.3390/ijms241310986.
[22]Dong F, Zheng L, Zhang X. Alpha-boswellic acid accelerates acute wound healing via NF-κB signaling pathway[J]. PLoS One, 2024, 19(9):030802-030803. DOI:10.1371/journal.pone.0308028.
[23]Zhang M, Chen H, Qian H, et al. Characterization of the skin keloid microenvironment[J]. Cell Commun Signal, 2023, 21(1):207-208. DOI:10.1186/s12964-023-01214-0.
[24]Li Q, Cheng F, Zhou K, et al. Increased sensitivity to TNF-α promotes keloid fibroblast hyperproliferation by activating the NF-κB, JNK and p38 MAPK pathways[J]. Exp Ther Med, 2021, 21(5):502-503. DOI:10.3892/etm.2021.9933.
[25]Chen Y, Gao Y, Zhang Z, et al. POSTN silencing ameliorates LL37-induced rosacea and inhibits the JAK2/STAT3 and NF-κB pathways[J]. FASEB J, 2025, 39(10):e70643-70643. DOI:10.1096/fj.202403202R.
[26]Zhu D, Wang Z, Chen S, et al. Therapeutic potential of targeting the IRF2/POSTN/Notch1 axis in nucleus pulposus cells for intervertebral disc degeneration[J].J Neuroinflammation,2025, 22(1):13. DOI:10.1186/s12974-025-03335-4.
[27]Shang Y, Liang Y, Zhang B, et al. Periostin-mediated activation of NF-on of NF-F- IL-1fferentiafferentiaia018 Dec;chemoresistance in glioblastoma[J]. Sci Rep, 2025, 15(1):13955-13956. DOI:10.1038/s41598-025-92969-8.