Glomerular podocytes are highly differentiated epithelial cells that are key 
components of the kidney filtration units. Podocyte damage or loss is the 
hallmark of nephritic diseases characterized by severe proteinuria. Recent 
studies implicate that hormones including glucocorticoids (ligand for 
glucocorticoid receptor) and vitamin D3 (ligand for vitamin D receptor) protect 
or promote repair of podocytes from injury. In order to elucidate the mechanisms 
underlying hormone-mediated podocyte-protecting activity from injury, we carried 
out microarray gene expression studies to identify the target genes and 
corresponding pathways in response to these hormones during podocyte 
differentiation. We used immortalized human cultured podocytes (HPCs) as a model 
system and carried out in vitro differentiation assays followed by dexamethasone 
(Dex) or vitamin D3 (VD3) treatment. Upon the induction of differentiation, 
multiple functional categories including cell cycle, organelle dynamics, 
mitochondrion, apoptosis and cytoskeleton organization were among the most 
significantly affected. Interestingly, while Dex and VD3 are capable of 
protecting podocytes from injury, they only share limited target genes and 
affected pathways. Compared to VD3 treatment, Dex had a broader and greater 
impact on gene expression profiles. In-depth analyses of Dex altered genes 
indicate that Dex crosstalks with a broad spectrum of signaling pathways, of 
which inflammatory responses, cell migration, angiogenesis, NF-κB and TGFβ 
pathways are predominantly altered. Together, our study provides new information 
and identifies several new avenues for future investigation of hormone signaling 
in podocytes.