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Am J Physiol Renal Physiol 287: F602-F611, 2004. First published June 8, 2004; doi:10.1152/ajprenal.00015.2004
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TRANSLATIONAL PHYSIOLOGY

Differential expression of collagen- and laminin-binding integrins mediates ureteric bud and inner medullary collecting duct cell tubulogenesis

Dong Chen,1 Richard Roberts,2 Martin Pohl,3 Sanjay Nigam,3 Jordan Kreidberg,4 Zemin Wang,4 Jyrki Heino,5 Johanna Ivaska,5 Sergio Coffa,1 Raymond C. Harris,1,6 Ambra Pozzi,1,6,7 and Roy Zent1,6,7

1Division of Nephrology, Department of Medicine, 2Department of Pathology, 7Department of Cancer Biology, Vanderbilt University Medical Center, and 6Veterans Affairs Hospital, Nashville, Tennessee 37232; 3Departments of Medicine and Pediatrics, University of California, La Jolla, California 92093; 4Department of Medicine, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; and 5MediCity Research Laboratory and the Department of Medical Biochemistry, University of Turku, Turku, Finland 20520

Submitted 15 January 2004 ; accepted in final form 1 June 2004

Inner medullary collecting ducts (IMCD) are terminally differentiated structures derived from the ureteric bud (UB). UB development is mediated by changes in the temporal and spatial expression of integrins and their respective ligands. We demonstrate both in vivo and in vitro that the UB expresses predominantly laminin receptors ({alpha}3{beta}1-, {alpha}6{beta}1-, and {alpha}6{beta}4-integrins), whereas the IMCD expresses both collagen ({alpha}1{beta}1- and {alpha}2{beta}1-integrins) and laminin receptors. Cells derived from the IMCD, but not the UB, undergo tubulogenesis in collagen-I (CI) gels in an {alpha}1{beta}1- and {alpha}2{beta}1-dependent manner. UB cells transfected with the {alpha}2-integrin subunit undergo tubulogenesis in CI, suggesting that collagen receptors are required for branching morphogenesis in CI. In contrast, both UB and IMCD cells undergo tubulogenesis in CI/Matrigel gels. UB cells primarily utilize {alpha}3{beta}1- and {alpha}6-integrins, whereas IMCD cells mainly employ {alpha}1{beta}1 for this process. These results demonstrate a switch in integrin expression from primarily laminin receptors in the early UB to both collagen and laminin receptors in the mature IMCD, which has functional consequences for branching morphogenesis in three-dimensional cell culture models. This suggests that temporal and spatial changes in integrin expression could help organize the pattern of branching morphogenesis of the developing collecting system in vivo.

kidney development; branching morphogenesis; three-dimensional culture; basement membranes


Address for reprint requests and other correspondence: R. Zent, Vanderbilt Medical Center North, Rm. C3210, MCN, Nashville, TN 37232 (E-mail: roy.zent{at}vanderbilt.edu)




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