Abstract
Purpose: :
Pax–2 is a member of Pax family of homeotic genes that encode nuclear transcription factor and plays an essential role in the development of vertebrate eyes, neural tube, otic system and kidney. Mutations in Pax–2 cause severe developmental disorders. Growth Factors like Bone Morphogenetic Proteins (BMP7), Sonic Hedgehog (Shh), and Fibroblast Growth Factors (FGFs) have an essential role in the development of the eye. The main purpose of our study is to understand their effect on Pax–2 expression and activity.
Methods: :
mIMCD–3 cells were grown as per the ATCC instructions in DMEM : F12 media supplemented with 10% FBS (Fetal Bovine Serum) and at 70%–80% confluence, they were shifted to serum free media for 8–10 hrs and then treated with BMP7, Sonic hedgehog and FGF–8 overnight. Total protein was isolated and western blotting was performed for Pax–2, activated phospho Pax–2 and JNK–1.
Results: :
BMP–7 and Shh either alone or together have marked effect on the expression of Pax–2 and phospho Pax–2 in vitro. BMP7, Shh and FGF8 increased the levels of phospho Pax2 which is also the activated form of Pax2. JNK1 expression decreased in presence of BMP7 which in turn was eliminated by Follistatin in presence of BMP7.
Conclusions: :
BMP7, Shh and FGF8 regulate the expression of Pax–2 either directly or indirectly. BMP7 and Shh are likely to have their effects through the same signaling pathway. BMP7 might be an antagonist of JNK as its expression is decreased in presence of BMP7.
Keywords: transcription factors • signal transduction • growth factors/growth factor receptors