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白细胞介素-10 通过抑制 TGF-β/Smad 通路对瘢痕成纤维细胞的治疗作用。

Therapeutic effect of interleukin-10 in keloid fibroblasts by suppression of TGF-β/Smad pathway.

机构信息

Dermatological Department, Qilu Children's Hospital of Shandong University, Jinan, Shandong, PR. China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):9085-9092. doi: 10.26355/eurrev_201910_19311.

Abstract

OBJECTIVE

Keloids are a skin disorder where the skin goes beyond the original border of the wound or trauma, resulting in functional and cosmetic deformities, displeasure, itching, pain, psychological stress, and patient dissatisfaction. This study aimed to explore the therapeutic effect of interleukin-10 (IL-10) on the proliferation of keloid fibroblasts.

PATIENTS AND METHODS

Keloid fibroblasts were isolated, primarily cultured, and treated with IL-10 at different concentrations. Normal skin fibroblasts were used as normal control. Immunofluorescent staining was performed to identify the establishment of keloid, as well as normal skin fibroblast. Cell Counting Kit-8 (CCK-8) was carried out to monitor the proliferative variation, while Western blot was conducted to detect the expression variation of key members involved in the TGF-β/Smad signaling pathway.

RESULTS

Identified by the IF staining of Vimentin, a classical biomarker of fibroblast, both primary culture of keloid and normal skin fibroblasts have been established. Compared with control, the proliferation of Keloid fibroblasts was shown to be significantly suppressed on treatment with IL-10 in a time and dose-dependent manner. Expression of P-Smad2/3 and Smad4 were increasingly down-regulated, whereas Smad-7 was up-regulated with the increasing concentration of IL-10. By contrast, the variation of Smad 2/3 expressions was hardly influenced. Furthermore, the Collagen Type I and Collagen Type II were found to be markedly decreased after treatment with IL-10.

CONCLUSIONS

IL-10 was shown to be able to significantly inhibit the proliferation of keloid fibroblasts, which was explicitly and strongly suggestive of its potential therapeutic effect in the management of keloid.

摘要

目的

瘢痕疙瘩是一种皮肤疾病,其特征是皮肤超出伤口或创伤的原始边界,导致功能和美容畸形、不适、瘙痒、疼痛、心理压力和患者不满。本研究旨在探讨白细胞介素-10(IL-10)对瘢痕疙瘩成纤维细胞增殖的治疗作用。

患者和方法

分离、原代培养瘢痕疙瘩成纤维细胞,并以不同浓度的 IL-10 进行处理。正常皮肤成纤维细胞作为正常对照。采用免疫荧光染色鉴定瘢痕疙瘩和正常皮肤成纤维细胞的建立。通过细胞计数试剂盒-8(CCK-8)检测监测增殖变化,同时通过 Western blot 检测 TGF-β/Smad 信号通路中关键成员的表达变化。

结果

通过波形蛋白(一种成纤维细胞的经典标志物)的免疫荧光染色鉴定,已成功建立了原代培养的瘢痕疙瘩和成纤维细胞。与对照组相比,IL-10 处理后,瘢痕疙瘩成纤维细胞的增殖呈时间和剂量依赖性显著抑制。随着 IL-10 浓度的增加,P-Smad2/3 和 Smad4 的表达逐渐下调,而 Smad-7 的表达上调。相比之下,Smad 2/3 的表达变化几乎不受影响。此外,经 IL-10 处理后,胶原 I 型和胶原 II 型明显减少。

结论

IL-10 能够显著抑制瘢痕疙瘩成纤维细胞的增殖,这明确且强烈提示其在瘢痕疙瘩治疗中的潜在治疗效果。

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