Juxtaglomerular (JG) cells, renin expressing cells of the renal afferent arterioles, have been described as modified vascular smooth muscle cells (VSMC). In response to prolonged stimulation, the number of renin producing cells in the JG afferent arterioles increases significantly. This phenomenon, known as JG cell hyperplasia, is thought to involve phenotypic change of afferent arteriole VSMC to become renin producing cells. However, recent studies have demonstrated that renin progenitor cells (RPC) can be detected in the mesenchyme of the prevascular metanephric kidney. These RPC are incorporated into the afferent arterioles of the embryonic kidney, become JG renin producing cells and acquire smooth muscle markers. Our recent data support these findings and demonstrate that adult mesenchymal stem cells (MSC) can be induced into renin synthesizing JG-like cells in vitro. Furthermore, MSC-like cells (characterized by CD44 and c-kit immunoreactivity) can be isolated from the adult kidney and can differentiate to express renin. Moreover, we have observed that JG cells undergoing hyperplasia in vivo (in response to low sodium diet and captopril) exhibit co-staining for renin, BrdU, CD44+ and c-kit+. Taken together, these data have led us to hypothesize that: 1) MSCs are precursors of JG renin producing cells, 2) MSC-like cells exist in the adult kidney in vivo and undergo proliferation and differentiation under intense stimulation and contribute to JG cell hyperplasia, and 3) these cells in the adult kidney may either be resident RPC or originate extrarenally. To examine these hypotheses, four specific aims will be undertaken: 1) we will first confirm that renin cells derived from MSCs in culture possess authentic JG cell characteristics;2) we will inject MSCs into mouse blastocysts and follow their fate in the kidney as they become renin expressing cells of the afferent arteriole during development and in the pathobiology of JG hyperplasia in the adult animal;3) we will further demonstrate that RPC with MSC characteristics exist in the kidney and that these cells can become JG renin cells and participate in JG hyperplasia;and 4) we will determine the source of these RPC in the adult kidney i.e. resident intrarenally vs. originating extrarenally such as the bone marrow. These experiments should lead to a greater understanding of the mechanisms of JG hyperplasia and the regulation of renin expression.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Pathobiology of Kidney Disease Study Section (PBKD)
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Thrasher, Terry N
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Duke University
Internal Medicine/Medicine
Schools of Medicine
United States
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