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从小鼠脂肪细胞直接重编程而来的真皮成纤维样细胞。

Dermal fibroblast-like cells reprogrammed directly from adipocytes in mouse.

作者信息

Toyosaki Mitsunobu, Homma Koichiro, Suzuki Sayuri, Muraoka Naoto, Hashimoto Hisayuki, Goshima Naoki, Ieda Masaki, Sasaki Junichi

机构信息

Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Department of Cardiology, Faculty of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

出版信息

Sci Rep. 2020 Dec 8;10(1):21467. doi: 10.1038/s41598-020-78523-8.

Abstract

In deep burns, early wound closure is important for healing, and skin grafting is mainly used for wound closure. However, it is difficult to achieve early wound closure in extensive total body surface area deep burns due to the lack of donor sites. Dermal fibroblasts, responsible for dermis formation, may be lost in deep burns. However, fat layers composed of adipocytes, lying underneath the dermis, are retained even in such cases. Direct reprogramming is a novel method for directly reprograming some cells into other types by introducing specific master regulators; it has exhibited appreciable success in various fields. In this study, we aimed to assess whether the transfection of master regulators (ELF4, FOXC2, FOXO1, IRF1, PRRX1, and ZEB1) could reprogram mouse adipocytes into dermal fibroblast-like cells. Our results indicated the shrinkage of fat droplets in reprogrammed mouse adipocytes and their transformation into spindle-shaped dermal fibroblasts. Reduced expression of PPAR-2, c/EBP, aP2, and leptin, the known markers of adipocytes, in RT-PCR, and enhanced expression of anti-ER-TR7, the known anti-fibroblast marker, in immunocytochemistry, were confirmed in the reprogrammed mouse adipocytes. The dermal fibroblast-like cells, reported here, may open up a new treatment mode for enabling early closure of deep burn wounds.

摘要

在深度烧伤中,早期伤口闭合对愈合很重要,皮肤移植主要用于伤口闭合。然而,由于缺乏供皮区,大面积全身体表面积深度烧伤很难实现早期伤口闭合。负责真皮形成的真皮成纤维细胞可能在深度烧伤中丢失。然而,即使在这种情况下,位于真皮下方由脂肪细胞组成的脂肪层仍会保留。直接重编程是一种通过引入特定的主调控因子将某些细胞直接重编程为其他类型细胞的新方法;它在各个领域都取得了显著成功。在本研究中,我们旨在评估主调控因子(ELF4、FOXC2、FOXO1、IRF1、PRRX1和ZEB1)的转染是否能将小鼠脂肪细胞重编程为真皮成纤维细胞样细胞。我们的结果表明,重编程后的小鼠脂肪细胞中脂滴缩小,并转化为纺锤形真皮成纤维细胞。在逆转录聚合酶链反应中,重编程后的小鼠脂肪细胞中已知的脂肪细胞标志物PPAR-2、c/EBP、aP2和瘦素的表达降低,在免疫细胞化学中,已知的抗成纤维细胞标志物抗ER-TR7的表达增强。本文报道的真皮成纤维细胞样细胞可能为实现深度烧伤伤口的早期闭合开辟一种新的治疗模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cfa/7722719/f9a3ef340a27/41598_2020_78523_Fig1_HTML.jpg

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