Effect of Epidermal Growth Factor on the Developing Rat Renal Papilla

Abstract

Background: Apoptosis plays an important role in the morphogenesis of the renal papilla. During kidney development, ATL is derived from the TAL in the inner medulla by apoptotic deletion of a fraction of TAL cells and the transformation of the remaining TAL cells. EGF is an important regulator of apoptosis in the kidney. Hypothesis: Exogenously administered EGF in postnatal rat affects renal papilla growth with cell proliferation and apoptosis in the loop of Henle. Methods: Rat pups received subcutaneous injections of EGF (0.3 µg/g body weight) or saline four times a day from after birth. Rats were sacrificed and the kidneys were preserved for immunohistochemistry on day 4 and day 7. The TAL was identified with antibody directed against Na-K-ATPase or BSC1, and type A intercalated cells were identified with antibody to anion exchanger 1 (AE1). Apoptosis was detected with TUNEL method, and cell proliferation with immunostaining for PCNA. Results – Primary and Secondary: EGF treatment resulted in the following: (1) reduced kidney weight; (2) shortened length of renal papilla; (3) delayed transformation of the cuboidal epithelium into the squamous epithelium of the ATL; (4) delayed elimination of type A intercalated cells in the medullary collecting duct; (5) decreased both apoptotic index and PCNA-positive cells in the TAL and the collecting duct of the renal medulla. Conclusion: These findings suggest that exogenous EGF delays the development of loop of Henle in the renal papilla by reducing both apoptosis and cell proliferation.