Knockdown of a disintegrin A metalloprotease 12 (ADAM12) during adipogenesis reduces cell numbers, delays differentiation, and increases lipid accumulation in 3T3-L1 cells

Molecular Biology of the Cell
Chantal A ColesJason D White

Abstract

Mouse models have shown that a disintegrin A metalloprotease 12 (ADAM12) is implicated during adipogenesis; the molecular pathways are not well understood. Stealth RNA interference was used to knock down ADAM12 in 3T3-L1 cells. Using gene profiling and metabolic enzymatic markers, we have identified signaling pathways ADAM12 impacts upon during proliferation, differentiation, and maturation of adipocytes. ADAM12 reduced cell numbers in proliferating preadipocytes, delayed differentiation of preadipocytes to adipocytes, and increased lipid accumulation in mature adipocytes. The pathway most affected by ADAM12 knockdown was regulation of insulin-like growth factor (IGF) activity by insulin-like growth factor binding proteins (IGFBPs); ADAM12 is known to cleave IGFBP3 and IGFBP5. The IGF/mTOR signaling pathway was down-regulated, supporting a role for ADAM12 in the IGFBP/IGF/mTOR-growth pathway. PPARγ signaling was also down-regulated by ADAM12 knockdown. Gene ontology (GO) analysis revealed that the extracellular matrix was the cellular compartment most impacted. Filtering for matrisome genes, connective tissue growth factor ( Ctgf) was up-regulated. CTGF and IGBP3 can interact with PPARγ to hinder its regulation. Increased expre...Continue Reading

References

Mar 1, 1985·The Biochemical Journal·M J Clemens, M A McNurlan
Oct 1, 1994·Molecular Reproduction and Development·P J HertzogI Kola
Apr 15, 1996·Genes & Development·R P BrunB M Spiegelman
Jun 27, 1998·The Journal of Biological Chemistry·F LoechelU M Wewer
Sep 1, 1999·The Journal of Endocrinology·K RajkumarL J Murphy
Oct 6, 1999·Current Opinion in Cell Biology·C Streuli
Jun 13, 2000·The Journal of Biological Chemistry·Z ShiL J Murphy
Nov 30, 2000·Biochemical and Biophysical Research Communications·F LoechelU M Wewer
Nov 1, 2001·Annual Review of Cell and Developmental Biology·M D Sternlicht, Z Werb
May 10, 2002·The American Journal of Pathology·Nobuko KawaguchiUlla M Wewer
Dec 6, 2002·Endocrine Reviews·Sue M Firth, Robert C Baxter
Dec 17, 2002·Molecular and Cellular Biology·Tomohiro KurisakiAtsuko Sehara-Fujisawa
Sep 24, 2004·The Journal of Biological Chemistry·Roopali RoyMarsha A Moses
Jan 8, 2005·Endocrinology·Megumi MasakiAtsuko Sehara-Fujisawa
May 18, 2005·Endocrine Reviews·Takashi Kadowaki, Toshimasa Yamauchi
Feb 4, 2006·The Journal of Biological Chemistry·Ulla M WewerReidar Albrechtsen
May 23, 2006·BMC Bioinformatics·Matthew E RitchieGordon K Smyth
Feb 24, 2007·Nature Reviews. Molecular Cell Biology·Andrea Page-McCawZena Werb
Aug 28, 2007·Bioinformatics·Matthew E RitchieGordon K Smyth
Mar 18, 2008·The International Journal of Biochemistry & Cell Biology·Marie KveiborgUlla M Wewer
May 9, 2008·American Journal of Physiology. Cell Physiology·Matthew P KrauseThomas J Hawke
Jul 4, 2008·American Journal of Physiology. Cell Physiology·Joanne T M TanStephen M Twigg
Jan 15, 2009·American Journal of Physiology. Endocrinology and Metabolism·Sophie S Y ChanRobert C Baxter
Mar 10, 2009·Trends in Endocrinology and Metabolism : TEM·Martina I Lefterova, Mitchell A Lazar
Mar 28, 2009·Biochemical and Biophysical Research Communications·Giovanna Zappalà, Matthew M Rechler
Oct 6, 2009·Trends in Endocrinology and Metabolism : TEM·Robert C Baxter, Stephen M Twigg
Jul 9, 2010·Bioinformatics·Di WuGordon K Smyth
Dec 14, 2011·Molecular & Cellular Proteomics : MCP·Alexandra NabaRichard O Hynes
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
May 29, 2012·Nucleic Acids Research·Di Wu, Gordon K Smyth
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth

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Methods Mentioned

BETA
gene knockdown
PCR

Software Mentioned

R
Bioconductor
SkanIt
limma
Genstat
Leica Microsystems QWin

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