SREBP-1c expression in Schwann cells is affected by diabetes and nutritional status.
Our previous work demonstrated that the sterol response element binding proteins (SREBP)-1 and SREBP-2, which are the key regulators of storage lipid and cholesterol metabolism respectively, are highly expressed in Schwann cells of adult peripheral nerves. In order to evaluate the role of Schwann cell SREBPs in myelination and functioning of peripheral nerves we have determined their expression during development, after fasting and refeeding, and in a rodent model of diabetes. Our results show that SREBP-1c and SREBP-2, unlike SREBP-1a, are the major forms of SREBPs present in peripheral nerves. The expression profile of SREBP-2 follows the expression of genes involved in cholesterol biosynthesis, while SREBP-1c is co-expressed with genes involved in storage lipid metabolism. In addition, the expression of SREBP-1c in the endoneurial compartment of peripheral nerves depends on nutritional status and is disturbed in type 1 diabetes. In line with this, insulin elevates the expression of SREBP-1c in primary cultured Schwann cells by activating the SREBP-1c promoter. Taken together, these findings reveal that SREBP-1c expression in Schwann cells responds to metabolic stimuli including insulin and that this response is affected in type 1 diabetes mellitus. This suggests that disturbed SREBP-1c regulated lipid metabolism may contribute to the pathophysiology of diabetic peripheral neuropathy.
de Preux
Anne-Sophie
AS
Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
Goosen
Katinka
K
Zhang
Weixian
W
Sima
Anders A F
AA
Shimano
Hitoshi
H
Ouwens
D Margriet
DM
Diamant
Michaela
M
Hillebrands
Jan-Luuk
JL
Rozing
Jan
J
Lemke
Greg
G
Beckmann
Jacques S
JS
Smit
August B
AB
Verheijen
Mark H G
MH
Chrast
Roman
R
D000818:Animals; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005215:Fasting; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D009752:Nutritional Status; D020411:Oligonucleotide Array Sequence Analysis; D010525:Peripheral Nerves / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D012584:Sciatic Nerve / Q000033:anatomy & histology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D007328:Insulin; D020033:Protein Isoforms; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2