Correspondence

Expression of Transforming Growth Factor (β)3 in Hypertrophic Juxtaglomerular Apparatus

N Engl J Med 1994; 330:68-69January 6, 1994

Article

To the Editor:

The mechanisms responsible for hypertrophy of the juxtaglomerular apparatus are not understood. We present histologic evidence to suggest that transforming growth factor β3 (TGF-β3), a multifunctional cytokine, may be regulated with renin and may have an important role in this hypertrophy.

A 16-month-old hypertensive child with renal failure treated with long-term peritoneal dialysis was referred for renal transplantation. The renal failure was due to renal-artery thrombosis of a solitary left kidney that occurred after percutaneous renal angioplasty. On admission, the patient had a blood pressure of 135/85 mm Hg and was receiving captopril, hydralazine, and propranolol. Plasma renin activity was elevated (72 ng per milliliter per hour; normal, <7) seven days after treatment with captopril was discontinued.

Ultrasonography revealed a small solitary left kidney (5.6 cm in length). Renal blood flow and glomerular filtration were not detected by [¹³¹I]iodohippurate and [⁹⁹Tc]pentetic acid scanning, respectively. The renal artery could not be cannulated during a preoperative angiogram, and a late-phase nephrogram was not available for study. A percutaneous renal biopsy revealed closely approximated glomeruli, tubular atrophy, mild arteriolosclerosis with marked intimal hyperplasia, and hypertrophy of vascular smooth-muscle and juxtaglomerular cells.

Immunohistochemical studies revealed intense staining for renin and the mature form of TGF-β3 in the juxtaglomerular apparatus (Figure 1Figure 1Renal Histologic Findings and Immunolocalization of Renin (Panel A) and TGF-β3 (Panel B) in a Child with Renal-Artery Stenosis.)1,2. In addition, antibody to the immature form of TGF-β3 stained all hypertrophic renal vascular smooth-muscle cells (not shown). A more diffuse, heterogeneous pattern of staining for TGF-β1 and TGF-β2 was seen in renal tubules. Localization of renin and both mature and immature forms of TGF-β3 was not seen in biopsy specimens from children with transplant rejection, acute tubular necrosis, or IgA nephropathy.

The β types of TGF have diverse biologic effects, including the control of cell growth, regulation of the synthesis of extracellular matrix protein, modification of cellular adhesion molecules, and control of local hormone systems3. TGF-β2 localizes with renin in the juxtaglomerular apparatus and renal vasculature when renin secretion is stimulated by dehydration4 or potassium depletion in mice and rats5. In this infant, we demonstrated localization of TGF-β3 and renin within the juxtaglomerular apparatus and in renal arterioles. This finding suggests that TGF-β3 may function as a local mediator of hypertrophy of the juxtaglomerular apparatus and renin secretion, at least under pathologic conditions such as renal-artery stenosis.

Patricio E. Ray, M.D.
National Institute of Dental Research, Bethesda, MD 20892

Bryan K. McCune, M.D.
Johns Hopkins School of Medicine, Baltimore, MD 21205

R. Ariel Gomez, M.D.
University of Virginia School of Medicine, Charlottesville, VA 22908

Edward J. Ruley, M.D.
Children's National Medical Center, Washington, DC 20010

Paul E. Klotman, M.D.
National Institute of Dental Research, Bethesda, MD 20892

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Citing Articles (5)

Citing Articles

1. 1

   Yufeng Huang, Wayne A. Border, Nancy A. Noble. (2007) Functional renin receptors in renal mesangial cells. Current Hypertension Reports 9:2, 133-139
   CrossRef

2. 2

   Y Huang, S Wongamorntham, J Kasting, D McQuillan, R T Owens, L Yu, N A Noble, W Border. (2006) Renin increases mesangial cell transforming growth factor-β1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms. Kidney International 69:1, 105-113
   CrossRef

3. 3

   Ray, Patricio E., Liu, Xue-Hui, , Inagami, Tadashi, , Chandra, Roma S., . (1998) Expression of Renin in Glomerular Nonjuxtaglomerular Cells in a Child with a Hypertensive Bartter's-Like Syndrome. New England Journal of Medicine 339:9, 632-634
   Full Text

4. 4

   Myriam Hanssens, Lisbeth Vercruysse, Lieve Verbist, Robert Pijnenborg, Marc J. N. C. Keirse, F. Andr Assche. (1995) Renin-like immunoreactivity in human placenta and fetal membranes. Histochemistry and Cell Biology 104:6, 435-442
   CrossRef

5. 5

   Magdi Shehata, Geoffrey H Cope, Tim S Johnson, Andrew T Raftery, A Meguid El Nahas. (1995) Cyclosporine enhances the expression of TGF-β in the juxtaglomerular cells of the rat kidney. Kidney International 48:5, 1487-1496
   CrossRef