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短暂丝裂霉素 C 处理人角膜上皮细胞和纤维母细胞可改变细胞迁移、细胞因子分泌和基质积累。

Transient Mitomycin C-treatment of human corneal epithelial cells and fibroblasts alters cell migration, cytokine secretion, and matrix accumulation.

机构信息

George Washington University School of Medicine and Health Sciences, Department of Anatomy and Cell Biology, 2300 I St. NW, Washington, DC, 20037, USA.

Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, 20 Staniford St, Boston, MA, 02114-2500, USA.

出版信息

Sci Rep. 2019 Sep 25;9(1):13905. doi: 10.1038/s41598-019-50307-9.

DOI:10.1038/s41598-019-50307-9
PMID:31554858
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6761181/
Abstract

A single application of Mitomycin C (MMC) is used clinically in ophthalmology to reduce scarring and enhance wound resolution after surgery. Here we show in vitro that a 3-hour MMC treatment of primary and telomerase immortalized human corneal limbal epithelial (HCLE) cells impacts their migration and adhesion. Transient MMC treatment induces HCLE expression of senescence associated secretory factors, cytokine secretion, and deposition of laminin 332 for several days. Transient MMC treatment also reduces migration and deposition of transforming growth factor-β1 (TGFβ1)-stimulated collagen by corneal fibroblasts. Using conditioned media from control and MMC treated cells, we demonstrate that factors secreted by MMC-treated corneal epithelial cells attenuate collagen deposition by HCFs whereas those secreted by MMC-treated HCFs do not. These studies are the first to probe the roles played by corneal epithelial cells in reducing collagen deposition by corneal fibroblasts in response to MMC.

摘要

临床上,丝裂霉素 C(MMC)单次应用可减少眼科手术后的瘢痕形成,促进伤口愈合。在此,我们体外研究发现,MMC 处理原代和端粒酶永生化人角膜缘上皮(HCLE)细胞 3 小时,会影响其迁移和黏附。短暂的 MMC 处理诱导 HCLE 表达衰老相关分泌表型因子、细胞因子分泌和层粘连蛋白 332 沉积数天。短暂的 MMC 处理还会减少转化生长因子-β1(TGFβ1)刺激的角膜成纤维细胞胶原的迁移和沉积。使用来自对照和 MMC 处理细胞的条件培养基,我们证明了由 MMC 处理的角膜上皮细胞分泌的因子可减弱 TGFβ1 刺激的胶原沉积,而由 MMC 处理的角膜成纤维细胞分泌的因子则不能。这些研究首次探讨了角膜上皮细胞在响应 MMC 时减少角膜成纤维细胞胶原沉积中所起的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/931d76893b93/41598_2019_50307_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/a638a96b3631/41598_2019_50307_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/80461c908fc5/41598_2019_50307_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/e3358b18cce8/41598_2019_50307_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/f5b73b536e4c/41598_2019_50307_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/8e221b054537/41598_2019_50307_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/af0af9462d79/41598_2019_50307_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/f6d04332ef9e/41598_2019_50307_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/931d76893b93/41598_2019_50307_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/a638a96b3631/41598_2019_50307_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/80461c908fc5/41598_2019_50307_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/e3358b18cce8/41598_2019_50307_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/f5b73b536e4c/41598_2019_50307_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/8e221b054537/41598_2019_50307_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/af0af9462d79/41598_2019_50307_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/f6d04332ef9e/41598_2019_50307_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/738a/6761181/931d76893b93/41598_2019_50307_Fig8_HTML.jpg

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