期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 15, 页码 12433-12444出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.342873
关键词
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资金
- National Institutes of Health through the NEI [R44 EY017497, R43 EY021045]
- TissueTech, Inc.
- Ocular Surface Research and Education Foundation, Miami, FL
- Arthritis Research United Kingdom [18472, 19489]
- Versus Arthritis [19489, 18472] Funding Source: researchfish
Recently, we reported HC-HA, a covalent complex formed between heavy chains (HCs) of inter-alpha -inhibitor (I alpha I) and hyaluronan (HA) by the catalytic action of tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6), is responsible for human amniotic membrane (AM) anti-inflammatory, anti-scarring, and anti-angiogenic actions. At the present time, the only well characterized source of I alpha I is serum being produced by the liver. This study showed that AM epithelial and stromal cells and stromal matrix all stained positively for HA, HC 1, 2, and 3, bikunin, and TSG-6. TSG-6 mRNA and protein were constitutively expressed by cultured AM epithelial and stromal cells without being up-regulated by TNF. In serum-free conditions, these cells expressed I alpha I, leading to the formation of HC-HA complex that contained both HC1 and HC2. In contrast, only HC1 was found in the HC-HA complex purified from AM. Local production of I alpha I, the HC-TSG-6 intermediate complex, and HC-HA were abolished when cells were treated with siRNA to HC1, HC2, bikunin (all of which impair the biosynthesis of I alpha I), or TSG-6 but not to HC3. Collectively, these results indicate that AM is another tissue in addition to the liver to constitutively produce I alpha I and that the HC-HA complex made by this tissue is different from that found at inflammatory sites (e. g. in asthma and arthritis) and in the matrix of the cumulus oocyte complex.
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