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Receptor tyrosine kinases-instructed release of its inhibitor from hydrogel to delay ovarian aging.

Abstract：

:Premature ovarian failure (POF) is the most frequently occurred disease in ovary. Direct inhibition of mammalian target of rapamycin (mTOR) activity can treat woman POF but brings adverse effects to women. Herein, by rational design of a hydrogelator Nap-Phe-Phe-Asp-Arg-Leu-Tyr-OH (Y) and co-assembling Y with an inhibitor of receptor tyrosine kinase (RTK, an upstream kinase of mTOR), Ala-Glu-Ala-Ala-Leu-Tyr-Lys-Asn-Leu-Leu-His-Ser-OH (Inh), to form hydrogel Gel Y + Inh, we develop a "smart" strategy of RTK-responsive disassembly of the hydrogel to release Inh. Release of Inh moderately inhibits the activity of mTOR and therefore delays ovarian aging. Oocyte and zygote experiments show that Gel Y + Inh improves both meiotic maturation of the oocytes and early embryonic development of the zygotes. In vivo animal experiments indicate that Gel Y + Inh effectively delays ovarian aging in aged mice by down regulation of mTOR activity, stimulation of ovaries to secrete estrogen and progesterone, and development of more antral follicles for reproduction. We expect that our new hydrogel Gel Y + Inh could be applied to treat woman POF, as well as delay ovarian aging, in clinic in the near future.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Shi Z,Li X,Wei M,Chen P,Zhang T,Ling X,Zhang J,Zhao C,Wang F,Liang G

doi

10.1016/j.biomaterials.2020.120536

subject

Has Abstract

pub_date

2020-11-16 00:00:00

pages

120536

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(20)30782-1

pub_type

杂志文章

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