Transforming growth factor α and epidermal growth factor expression in experimental murine polycystic kidney disease
- 22 Downloads
Cystic change in polycystic kidney disease (PKD) is associated with epithelial hyperplasia, altered fluid and electrolyte transport, and de-differentiation of renal tubular epithelium. The role of polypeptide growth factors as potential modulators of cystic change remains an area of controversy. In this study, the expression of epidermal growth factor (EGF) and transforming growth factor-α (TGFα) were assessed by immunohistochemistry and image analysis in glucocorticoid-induced PKD in the newborn mouse. Newborn C3H mice received either 200 mg/kg methylprednisolone acetate (MPA) or 0.9% saline as a control. EGF expression was not detected in significant quantities in either MPA-treated or control animals. TGFα, however, was expressed in immature control kidney in a largely basolateral distribution. Expression increased significantly in association with cystic change in MPA-treated animals and was localized to the apical cell surface, implying altered polarity of secretion. There is no evidence that EGF is a mitogen in this early developmental model of PKD. TGFα, however, may be an important mediator of cystic change in immature or de-differentiated renal tubular epithelium.
Key wordsPolycystic kidneys Mouse Epidermal growth factor Transforming growth factor-α Glucocorticoids
Unable to display preview. Download preview PDF.
- 1.Grantham JJ (1993) Fluid secretion, cellular proliferation, and the pathogenesis of renal cysts. J Am Soc Nephrol 3: 1843–1857Google Scholar
- 12.Derynck R (1988) Transforming growth factor alpha. Cell 54: 593–595Google Scholar
- 15.Lowden DA, Lindemann GW, Merlino G, Barash BD, Calvet JP, Gattone VH II (1993) Renal cysts in transgenic mice expressing transforming growth factor alpha. J Lab Clin Med 124: 320–321Google Scholar
- 19.Ogborn MR, Sareen S (1995) Immunohistochemical detection of epidermal growth factor in plastic embedded tissues. Biotechnic Histochem 70: 202–204Google Scholar
- 20.Frigo B, Scopsi L, Patriarca C, Rilke F (1991) Silver enhancement of nickel-diaminobenzidine as applied to single and double immunoperoxidase staining. Biotechnic Histochem 66: 159–166Google Scholar
- 21.Gattone VH, Sherman DA, Hinton DA, Fu-wen N, Topham RT, Klein RM (1991) Epidermal growth factor in the neonatal mouse salivary gland and kidney. Biol Neonate 61: 54–67Google Scholar
- 23.North D, Lakshmanan J, Reviczky A, Kaser M, Fisher DA (1992) Ontogeny of epidermal growth factor, transforming grwoth factor-alpha, epidermal growth factor receptor, and thyroid hormone receptor RNA levels in rat kidney and changes in those levels induced by early thyroxine treatment. Pediatr Res 31: 330–334PubMedGoogle Scholar
- 28.Argilés A, Kraft N, Ootaka T, Hutchinson P, Atkins RC (1992) Epidermal growth factor and transforming growth factor-alpha stimulate or inhibit proliferation of a human renal adenocarcinoma cell line depending on cell status: differentiation of the two pathways by G protein involvement. Cancer Res 52: 4356–4360PubMedGoogle Scholar
- 30.Ogborn MR, Sareen S (1993) Epidermal growth factor (EGF) and transforming growth factor α (TGFα) expression in experimental murine neonatal polycystic kidney disease (PKD) (abstract). J Am Soc Nephrol 4: 473Google Scholar