Dataset Information

Adult renal mesenchymal stem cell-like cells contribute to juxtaglomerular cell recruitment.

ABSTRACT: The renin-angiotensin-aldosterone system (RAAS) regulates BP and salt-volume homeostasis. Juxtaglomerular (JG) cells synthesize and release renin, which is the first and rate-limiting step in the RAAS. Intense pathologic stresses cause a dramatic increase in the number of renin-producing cells in the kidney, termed JG cell recruitment, but how this occurs is not fully understood. Here, we isolated renal CD44(+) mesenchymal stem cell (MSC)-like cells and found that they differentiated into JG-like renin-expressing cells both in vitro and in vivo. Sodium depletion and captopril led to activation and differentiation of these cells into renin-expressing cells in the adult kidney. In summary, CD44(+) MSC-like cells exist in the adult kidney and can differentiate into JG-like renin-producing cells under conditions that promote JG cell recruitment.

SUBMITTER: Wang H

PROVIDER: S-EPMC3736701 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Adult renal mesenchymal stem cell-like cells contribute to juxtaglomerular cell recruitment.

Wang Hao H Gomez Jose A JA Klein Sabine S Zhang Zhiping Z Seidler Barbara B Yang Yanqiang Y Schmeckpeper Jeffrey J Zhang Lunan L Muramoto Garrett G GG Chute John J Pratt Richard E RE Saur Dieter D Mirotsou Maria M Dzau Victor J VJ

Journal of the American Society of Nephrology : JASN 20130606 8

The renin-angiotensin-aldosterone system (RAAS) regulates BP and salt-volume homeostasis. Juxtaglomerular (JG) cells synthesize and release renin, which is the first and rate-limiting step in the RAAS. Intense pathologic stresses cause a dramatic increase in the number of renin-producing cells in the kidney, termed JG cell recruitment, but how this occurs is not fully understood. Here, we isolated renal CD44(+) mesenchymal stem cell (MSC)-like cells and found that they differentiated into JG-lik ...[more]

PMID: 23744888

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Project description:Metastatic dissemination of solid tumors is often initiated by reactivation of an embryonic development program, epithelial-to-mesenchymal-transition (EMT). EMT has been associated with acquiring invasiveness and resistance to conventional therapies. However, the precise role of EMT during renal cell carcinoma is still debatable and is under investigation. In this context, our study is designed to evaluate the role of cyclosporine (CsA) and transforming growth factor-? (TGF?) administration in inducing EMT-like state in renal carcinoma cells. We also studied the associated phenotypic changes which may lead to tumor metastasis.The morphological changes in renal cell carcinoma cells (A498) treated with TGF-?/CsA were observed by microscopy. Atomic force microscope was used to evaluate the changes in elasticity of cells treated with TGF-?/CsA. The expression of mesenchymal and chemoresistance genes were checked by RT-PCR. Assays for migration, invasion, sphere formation ability and expression of cancer stem cell-like phenotypes were done to evaluate the metastatic potential of these cells. Lineage specific differentiations were also done to determine the acquisition of stem-cell like phenotype.Our results showed that treatment with TGF-?/CsA led to loss of epithelial characteristics and gain of mesenchymal phenotype in vitro. Changes in shape and elastic properties of the cancer cells favoured metastatic progression, increased tumorisphere formation and invasiveness post treatment. We also observed higher expression of chemoresistance and stemness markers in EMT-induced cells. These cells also differentiated to various lineages like osteoblasts, adipocytes, neural and hepatic cells when induced with the respective differentiation media.We concluded that TGF-?/CsA treatment led to acquisition of EMT-like cancer stem cells phenotype that enhanced local invasion and dissemination of renal carcinoma cells. This subpopulation of cells with EMT-like phenotype a can provide a better perception of the metastatic process. This can provide an in vitro system for testing pharmaceuticals for modulating EMT as a viable strategy within the therapeutic armamentarium for RCC patients. The results of our findings also suggest that CsA directly induced EMT like changes in epithelial cell which may be responsible for the potential risk of malignancy in transplant patients.

Dataset Information

Adult renal mesenchymal stem cell-like cells contribute to juxtaglomerular cell recruitment.

Publications

Adult renal mesenchymal stem cell-like cells contribute to juxtaglomerular cell recruitment.

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