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Prostaglandin F2α induces the normoxic activation of the hypoxia‐inducible factor‐1 transcription factor in differentiating 3T3‐L1 preadipocytes: Potential role in the regulation of adipogenesis
Author(s) -
Liu Li,
Clipstone Neil A.
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21801
Subject(s) - adipogenesis , transcription factor , gene knockdown , paracrine signalling , adipocyte , chemistry , microbiology and biotechnology , medicine , endocrinology , g alpha subunit , hypoxia inducible factors , biology , protein subunit , receptor , adipose tissue , biochemistry , apoptosis , gene
Prostaglandin F2α (PGF2α) is a potent paracrine inhibitor of adipocyte differentiation. Here we show that treatment of differentiating 3T3‐L1 preadipocytes with PGF2α induces the expression of DEC1, a transcriptional repressor that has previously been implicated in the inhibition of adipogenesis in response to hypoxia as a downstream effector of the hypoxia‐inducible factor‐1 (HIF‐1) transcription factor. Surprisingly, despite performing our experiments under normal ambient oxygen conditions, we find that treatment of differentiating 3T3‐L1 preadipocytes with PGF2α also results in the marked activation of HIF‐1, as measured by an increase in the accumulation of the HIF‐1α regulatory subunit. However, unlike the effects of hypoxia, this PGF2α‐induced normoxic increase in HIF‐1α is not mediated by an increase in the stability of the HIF‐1α polypeptide, rather we find that PGF2α selectively increases the expression of the alternatively spliced HIF‐1α I.1 mRNA isoform. Significantly, we demonstrate that the shRNA‐mediated knockdown of endogenous HIF‐1α expression attenuates the PGF2α‐induced expression of DEC1, overcomes the inhibitory effects of PGF2α on the expression of proadipogenic transcription factors C/EBPα and PPARγ and partially rescues the PGF2α‐induced inhibition of adipogenesis. Taken together, these results indicate that PGF2α promotes the activation of the HIF‐1 transcription factor pathway under normal oxygen conditions, and highlight a potential role for the normoxic activation of the HIF‐1/DEC1‐pathway in mediating the inhibitory effects of PGF2α on adipocyte differentiation. J. Cell. Biochem. 105: 89–98, 2008. © 2008 Wiley‐Liss, Inc.