CEMIP induces TGF-β/Smad signaling to promote keloid development by binding to SPARC.

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL Clinics Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI:10.1016/j.clinsp.2024.100523

Xinyi Li, Wei Zhang, Xiaojing Li

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Abstract

Background: Cell Migration Inducing Hyaluronidase 1 (CEMIP) is a protein that plays regulatory functions in a variety of cellular processes in many diseases. Nevertheless, its role and molecular mechanism in keloid hyperplasia are still elusive.

Methods: Expressions of CEMIP and Secreted Protein acidic and Rich in Cysteine (SPARC) were detected by qRT-PCR and western blot. CCK-8 assay, along with immunofluorescence staining, was applied for the assessment of cell proliferation. The capabilities of cells to migrate and invade were evaluated utilizing wound healing and Transwell, while Extracellular Matrix (ECM) deposition was measured by immunofluorescence and western blot. The interaction of CEMIP and SPARC was predicted by the Coexpedia and PPA-red databases and verified by co-IP. Western blot was adopted for the estimation of TGF-β/Smad pathway-related proteins.

Results: The data demonstrated that CEMIP expression was elevated in Keloid Fibroblasts (KF). CEMIP interference suppressed cell proliferative, migrative and invasive capabilities and ECM deposition in KF. Mechanistically, bioinformatics analysis revealed that CEMIP was co-expressed with SPARC and CEMIP protein could bind to SPARC. SPARC expression was reduced in CEMIP-silenced cells. SPARC overexpression counteracted the impacts of CEMIP silencing on cell proliferative, migrative and invasive capabilities and ECM deposition in KF. In addition, the expressions of TGF-β/Smad signaling-related proteins were decreased by CEMIP silencing via the inhibition of SPARC.

Conclusion: In summary, this study revealed that CEMIP modulated KF proliferation, migration, invasion and ECM deposition by TGF-β/Smad signaling through binding to SPARC.

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CEMIP 通过与 SPARC 结合，诱导 TGF-β/Smad 信号，促进瘢痕发育。

背景：细胞迁移诱导透明质酸酶1（CEMIP）是一种蛋白质，在许多疾病的多种细胞过程中发挥调控功能。然而，它在瘢痕疙瘩增生症中的作用和分子机制仍难以捉摸：方法：通过 qRT-PCR 和 western 印迹检测 CEMIP 和富含半胱氨酸的分泌蛋白（SPARC）的表达。CCK-8测定和免疫荧光染色被用于评估细胞增殖。利用伤口愈合和 Transwell 评估了细胞迁移和侵袭的能力，并通过免疫荧光和 Western 印迹检测了细胞外基质（ECM）的沉积。CEMIP和SPARC的相互作用由Coexpedia和PPA-red数据库预测，并通过co-IP验证。结果表明，CEMIP和SPARC之间的相互作用通过Coexpedia和PPA-red数据库进行预测，并通过co-IP进行验证；Western印迹用于评估TGF-β/Smad通路相关蛋白：结果：数据表明，CEMIP在瘢痕疙瘩成纤维细胞（KF）中表达升高。干扰 CEMIP 可抑制 KF 的细胞增殖、迁移和侵袭能力以及 ECM 沉积。生物信息学分析表明，CEMIP与SPARC共表达，CEMIP蛋白可与SPARC结合。在 CEMIP 沉默的细胞中，SPARC 的表达量减少。SPARC 的过表达抵消了 CEMIP 沉默对 KF 细胞增殖、迁移和侵袭能力以及 ECM 沉积的影响。此外，通过抑制 SPARC，沉默 CEMIP 可减少 TGF-β/Smad 信号相关蛋白的表达：综上所述，本研究揭示了 CEMIP 通过与 SPARC 结合，通过 TGF-β/Smad 信号调节 KF 的增殖、迁移、侵袭和 ECM 沉积。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinics 医学-医学：内科

CiteScore

4.10

自引率

3.70%

发文量

129

审稿时长

52 days

期刊介绍： CLINICS is an electronic journal that publishes peer-reviewed articles in continuous flow, of interest to clinicians and researchers in the medical sciences. CLINICS complies with the policies of funding agencies which request or require deposition of the published articles that they fund into publicly available databases. CLINICS supports the position of the International Committee of Medical Journal Editors (ICMJE) on trial registration.