A role for enhanced integrin and FAK expression in uremia-induced parathyroid hyperplasia.
Parathyroid (PT) hyperplasia is a major feature of secondary hyperparathyroidism (SH) in uremia. The transforming growth factor-alpha (TGFalpha) / epidermal growth factor receptor (EGFR)Ethgrowth loop is the main contributor to uremia-induced PT hyperplasia. Since integrin beta1 and focal adhesion kinase (FAK) are known to directly activate cell growth and enhance EGFR-driven growth, these studies examined their contribution to PT hyperplasia in uremia. Western blot analysis was used to measure the expression of EGFR, integrin beta1, and the non-receptor integrin-sensitive FAK, in PT glands from 8 hemodialysis patients with various degrees of SH at the time of the surgery, and in a normal human PT gland. In all patients, PT EGFR expression was higher than in the normal control. Integrin beta1, a direct activator of EGFR-driven growth, was increased in 5 of the 8 hyperplastic glands, whereas 7 out of 8 PT glands showed a marked enhancement in FAK expression, an elevation unrelated to increases in integrin beta1, but directly associated to time in hemodialysis. Similar increases in PT FAK content were observed after 1 month after the onset of uremia by 5/6 nephrectomy in rats. These findings suggest that in kidney disease, the increased PT cell growth driven by enhanced EGFR could be further aggravated through elevations in integrin beta1 and FAK expression.
Arcidiacono
Maria Vittoria
MV
Pharmacological Laboratories, Department of Medicine, Surgery, and Dentistry, San Paolo Hospital, University of Milan, Milan, Italy.
Cozzolino
Mario
M
Brancaccio
Diego
D
Gallieni
Maurizio
M
Lesma
Elena
E
Carelli
Stephana
S
Gorio
Alfredo
A
Di Giulio
Anna Maria
AM
D000368:Aged; D000818:Animals; D015153:Blotting, Western; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications / Q000628:therapy; D006965:Hyperplasia; D019012:Integrin beta1 / Q000378:metabolism*; D008875:Middle Aged; D010279:Parathyroid Diseases / Q000378:metabolism* / Q000473:pathology; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D006435:Renal Dialysis; D014511:Uremia / Q000150:complications* / Q000628:therapy
D019012:Integrin beta1; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases