Transforming growth factor-β regulates the expression of anosmin (KAL-1) in human retinal pigment epithelial cells.
In a microarray analysis of human retinal pigment epithelial cells (HRPE) treated with TGF-β, in addition to the alteration of a number of known Extracellular matrix (ECM)-related genes regulated by TGF-β, we found a significant increase in the expression of Kallmann Syndrome (KAL)-1 gene, that codes for the protein anosmin-1. Enhanced expression of KAL-1 by TGF-β was validated by real-time PCR analysis. In in vitro experiments, TGF-β receptor inhibitor abolished TGF-β-induced expression of KAL-1. Immunofluorescence staining showed increased presence of anosmin-1 in TGF-β treated HRPE cells, with distinct localization at the intercellular junctions. Treatment of HRPE cells with TGF-β enhanced secretion of anosmin-1 and the release of anosmin-1 was further augmented by heparin sulfate. Enhanced secretion of anosmin-1 in the presence of TGF-β and heparin was also observed in other ocular cells such as corneal epithelial and corneal fibroblast cultures. The role of anosmin-1, a protein with adhesion functions, in retinal structure, function and pathology has not been known and remains to be investigated.
Department of Surgery, University of Alabama, Birmingham, AL 35294-0019, United States. RRaju@uab.edu
Raghavan
R
Raju
Bixi
B
Jian
John J
JJ
Hooks
Chandrasekharam N
CN
Nagineni
D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D016212:Transforming Growth Factor beta