Serum deprivation protein response intervenes in the proliferation, motility, and extracellular matrix production in keloid fibroblasts by blocking the amplification of TGF-β1/SMAD signal cascade via ERK1/2.

Autor: Li P; Department of Burns and Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University (Jinan Central Hospital), No. 105 Jiefang Road, Jinan, Shandong 250013, PR China., Han M; Department of Burns and Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University (Jinan Central Hospital), No. 105 Jiefang Road, Jinan, Shandong 250013, PR China., Wang L; Department of Burns and Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University (Jinan Central Hospital), No. 105 Jiefang Road, Jinan, Shandong 250013, PR China., Gao C; Department of Burns and Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University (Jinan Central Hospital), No. 105 Jiefang Road, Jinan, Shandong 250013, PR China. Electronic address: 15553156228@163.com.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Aug; Vol. 489, pp. 117012. Date of Electronic Publication: 2024 Jun 19.
DOI: 10.1016/j.taap.2024.117012
Abstrakt: Keloid formation has been linked to abnormal fibroblast function, such as excessive proliferation and extracellular matrix (ECM) production. Serum deprivation protein response (SDPR) is a crucial regulator of cellular function under diverse pathological conditions, yet its role in keloid formation remains unknown. The current work investigated the function of SDPR in regulating the proliferation, motility, and ECM production of keloid fibroblasts (KFs), as well as to decipher the mechanisms involved. Analysis of RNA sequencing data from the GEO database demonstrated significant down-regulation of SDPR in KF compared to normal fibroblasts (NFs). This down-regulation was also observed in clinical keloid specimens and isolated KFs. Overexpression of SDPR suppressed the proliferation, motility, and ECM production of KFs, while depletion of SDPR exacerbated the enhancing impact of TGF-β1 on the proliferation, motility, and ECM production of NFs. Mechanistic studies revealed that SDPR overexpression repressed TGF-β/Smad signal cascade activation in KFs along with decreased levels of phosphorylated Samd2/3, while SDPR depletion exacerbated TGF-β/Smad activation in TGF-β1-stimulated NFs. SDPR overexpression also repressed ERK1/2 activation in KFs, while SDPR depletion exacerbated ERK1/2 activation in TGF-β1-stimulated NFs. Inhibition of ERK1/2 abolished SDPR-depletion-induced TGF-β1/Smad activation, cell proliferation, motility, and ECM production in NFs. In conclusion, SDPR represses the proliferation, motility, and ECM production in KFs by blocking the TGF-β1/Smad pathway in an ERK1/2-dependent manner. The findings highlight the role of SDPR in regulating abnormal behaviors of fibroblasts associated with keloid formation and suggest it as a potential target for anti-keloid therapy development.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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