Smad7 is a transforming growth factor-beta–inducible mediator of apoptosis in granulosa cells

Overexpression of Smad7 induces increased apoptosis, whereas decreased Smad7 expression reduces apoptosis induced by TGF-b in granulosa cells.

0
0
Like 0 Comment

Authors

Marisol Quezada, Ph.D., Jikui Wang, Ph.D., Valerie Hoang, M.S., Elizabeth A. McGee, M.D.

Vol 97, Issue 6 , Pages 1452-1459.e6

Abstract

Objective:

To determine the functional role of Smad7 in granulosa cells.

Design:

Granulosa cell culture and molecular biological techniques were used to investigate regulation and function of Smad7.

Setting:

Research laboratory.

Animal(s):

C57bl/j hybrid mouse.

Intervention(s):

Primary mouse granulosa cells were isolated and grown in culture for all messenger RNA expression experiments. Smad7 promoter constructs were evaluated with a luciferase reporter system in SIGC cells to determine sites activating Smad7 expression.

Main Outcome Measure(s):

Overexpression (Smad7 complementary DNA) and downregulation (Smad7 small interfering RNA) of Smad7 in primary mouse granulosa cells were used to evaluate the functional role of Smad7 in granulosa cells.

Result(s):

Smad7 expression was upregulated by treatment with transforming growth factor-β (TGF-β) but not activin or activation of the cyclic adenosine monophosphate pathway. The promoter of Smad7 was activated by TGF-β. Truncation of the promoter or mutation of the Smad response element at −141 eliminated TGF-β activation of the promoter. Smad3 was not specifically required for TGF-β–stimulated expression of Smad7, though activation of the TGFBR1 receptor was. When Smad7 was overexpressed in granulosa cells, apoptosis was markedly increased. When Smad7 expression was reduced with small interfering RNA, then the TGF-β–induced apoptosis was blocked.

Conclusion(s):

Smad7 mediates apoptosis induced by TGF-β in mouse granulosa cells, suggesting that dysregulation of Smad7 could impair folliculogenesis.

Read the full text at: http://www.fertstert.org/article/S0015-0282(12)00360-3/fulltext


Go to the profile of Fertility and Sterility

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

No comments yet.