Myofibroblasts in experimental hydronephrosis.
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Journal: 1995/March - American Journal of Pathology
ISSN: 0002-9440
PUBMED: 7856721
Abstract:
Interstitial fibrosis is a common outcome of longterm ureteral obstruction. One pathological arm of the fibrotic reaction in diverse tissue loci and experimental models is the retraction of granulation tissue. The role of the myofibroblast in granulation tissue contraction and fibrocontractive diseases has been well established, but the mechanisms leading to differentiation of fibroblastic cells into myofibroblasts during the evolution of inflammation are not yet fully clarified. Investigators using other model systems have shown that macrophage-derived transforming growth factor-beta 1 (TGF-beta 1) may be pivotal in the process of myofibroblast modulation. Our laboratory has shown that the unilateral ureteral obstruction in the rat is characterized by a 20-fold increment in infiltrating renal cortical interstitial macrophages, an increase in cortical TGF-beta 1 gene expression, which parallels the infiltrating macrophage burden, and immunolocalization of this peptide growth factor in close proximity to resident interstitial fibroblasts. Because of this model's features, it was our aim to assess whether a myofibroblastic modulation was operant in the renal cortex of obstructed rat kidneys versus the control contralateral unobstructed kidney specimens. Immunolabeling for alpha-smooth muscle actin and the intermediate filament protein, desmin, was detected and steadily intensified from 24 to 96 hours after unilateral ureteral obstruction in obstructed kidneys only. In temporal concert with the detection of alpha-smooth muscle actin protein, the mRNA expression for this cytoskeletal component exhibited 3.7-, 15.7-, and 4.1-fold increments in the renal cortex of obstructed kidneys versus the contralateral unobstructed kidney specimens at 24, 48, and 96 hours after unilateral ureteral obstruction, respectively. Whole body X-irradiation, administered to rats 11 days before proximal left ureteral ligation, significantly lowered cortical interstitial macrophage number, cortical TGF-beta and alpha-smooth muscle actin mRNA levels as well as the intensity of immunolabeling for alpha-smooth muscle actin from 12 to 96 hours after unilateral ureteral obstruction. These data support a postulate that renal cortical TGF-beta 1, derived from the infiltrating macrophage, in part, contributes to the subsequent interstitial fibrosis response to renal injury by fostering the modulation of fibroblasts to myofibroblasts within the renal cortex after ureteral obstruction.
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Am J Pathol 146(1): 121-129
PMID: 7856721

Myofibroblasts in experimental hydronephrosis.

Abstract

Interstitial fibrosis is a common outcome of longterm ureteral obstruction. One pathological arm of the fibrotic reaction in diverse tissue loci and experimental models is the retraction of granulation tissue. The role of the myofibroblast in granulation tissue contraction and fibrocontractive diseases has been well established, but the mechanisms leading to differentiation of fibroblastic cells into myofibroblasts during the evolution of inflammation are not yet fully clarified. Investigators using other model systems have shown that macrophage-derived transforming growth factor-beta 1 (TGF-beta 1) may be pivotal in the process of myofibroblast modulation. Our laboratory has shown that the unilateral ureteral obstruction in the rat is characterized by a 20-fold increment in infiltrating renal cortical interstitial macrophages, an increase in cortical TGF-beta 1 gene expression, which parallels the infiltrating macrophage burden, and immunolocalization of this peptide growth factor in close proximity to resident interstitial fibroblasts. Because of this model's features, it was our aim to assess whether a myofibroblastic modulation was operant in the renal cortex of obstructed rat kidneys versus the control contralateral unobstructed kidney specimens. Immunolabeling for alpha-smooth muscle actin and the intermediate filament protein, desmin, was detected and steadily intensified from 24 to 96 hours after unilateral ureteral obstruction in obstructed kidneys only. In temporal concert with the detection of alpha-smooth muscle actin protein, the mRNA expression for this cytoskeletal component exhibited 3.7-, 15.7-, and 4.1-fold increments in the renal cortex of obstructed kidneys versus the contralateral unobstructed kidney specimens at 24, 48, and 96 hours after unilateral ureteral obstruction, respectively. Whole body X-irradiation, administered to rats 11 days before proximal left ureteral ligation, significantly lowered cortical interstitial macrophage number, cortical TGF-beta and alpha-smooth muscle actin mRNA levels as well as the intensity of immunolabeling for alpha-smooth muscle actin from 12 to 96 hours after unilateral ureteral obstruction. These data support a postulate that renal cortical TGF-beta 1, derived from the infiltrating macrophage, in part, contributes to the subsequent interstitial fibrosis response to renal injury by fostering the modulation of fibroblasts to myofibroblasts within the renal cortex after ureteral obstruction.

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Selected References

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  • Klahr S. New insights into the consequences and mechanisms of renal impairment in obstructive nephropathy. Am J Kidney Dis. 1991 Dec;18(6):689–699. [PubMed] [Google Scholar]
  • Kaneto H, Morrissey J, Klahr S. Increased expression of TGF-beta 1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation. Kidney Int. 1993 Aug;44(2):313–321. [PubMed] [Google Scholar]
  • Walton G, Buttyan R, Garcia-Montes E, Olsson CA, Hensle TW, Sawczuk IS. Renal growth factor expression during the early phase of experimental hydronephrosis. J Urol. 1992 Aug;148(2 Pt 2):510–514. [PubMed] [Google Scholar]
  • Sharma AK, Mauer SM, Kim Y, Michael AF. Interstitial fibrosis in obstructive nephropathy. Kidney Int. 1993 Oct;44(4):774–788. [PubMed] [Google Scholar]
  • Diamond JR, Kees-Folts D, Ding G, Frye JE, Restrepo NC. Macrophages, monocyte chemoattractant peptide-1, and TGF-beta 1 in experimental hydronephrosis. Am J Physiol. 1994 Jun;266(6 Pt 2):F926–F933. [PubMed] [Google Scholar]
  • Massagué J. The transforming growth factor-beta family. Annu Rev Cell Biol. 1990;6:597–641. [PubMed] [Google Scholar]
  • Ding G, Pesek-Diamond I, Diamond JR. Cholesterol, macrophages, and gene expression of TGF-beta 1 and fibronectin during nephrosis. Am J Physiol. 1993 Apr;264(4 Pt 2):F577–F584. [PubMed] [Google Scholar]
  • Yamamoto T, Noble NA, Miller DE, Border WA. Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis. Kidney Int. 1994 Mar;45(3):916–927. [PubMed] [Google Scholar]
  • Jones CL, Buch S, Post M, McCulloch L, Liu E, Eddy AA. Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int. 1991 Dec;40(6):1020–1031. [PubMed] [Google Scholar]
  • Gabbiani G. The biology of the myofibroblast. Kidney Int. 1992 Mar;41(3):530–532. [PubMed] [Google Scholar]
  • Desmoulière A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 1993 Jul;122(1):103–111.[PMC free article] [PubMed] [Google Scholar]
  • Rubbia-Brandt L, Sappino AP, Gabbiani G. Locally applied GM-CSF induces the accumulation of alpha-smooth muscle actin containing myofibroblasts. Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;60(2):73–82. [PubMed] [Google Scholar]
  • Sappino AP, Schürch W, Gabbiani G. Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest. 1990 Aug;63(2):144–161. [PubMed] [Google Scholar]
  • Vyalov S, Desmoulière A, Gabbiani G. GM-CSF-induced granulation tissue formation: relationships between macrophage and myofibroblast accumulation. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993;63(4):231–239. [PubMed] [Google Scholar]
  • Diamond JR, Pesek-Diamond I. Sublethal X-irradiation during acute puromycin nephrosis prevents late renal injury: role of macrophages. Am J Physiol. 1991 Jun;260(6 Pt 2):F779–F786. [PubMed] [Google Scholar]
  • Pesek-Diamond I, Ding G, Frye J, Diamond JR. Macrophages mediate adverse effects of cholesterol feeding in experimental nephrosis. Am J Physiol. 1992 Nov;263(5 Pt 2):F776–F783. [PubMed] [Google Scholar]
  • Dijkstra CD, Döpp EA, Joling P, Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599.[PMC free article] [PubMed] [Google Scholar]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed] [Google Scholar]
  • McHugh KM, Lessard JL. The nucleotide sequence of a rat vascular smooth muscle alpha-actin cDNA. Nucleic Acids Res. 1988 May 11;16(9):4167–4167.[PMC free article] [PubMed] [Google Scholar]
  • Bochaton-Piallat ML, Gabbiani F, Ropraz P, Gabbiani G. Cultured aortic smooth muscle cells from newborn and adult rats show distinct cytoskeletal features. Differentiation. 1992 Apr;49(3):175–185. [PubMed] [Google Scholar]
  • Wallenstein S, Zucker CL, Fleiss JL. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. [PubMed] [Google Scholar]
  • Johnson RJ, Iida H, Alpers CE, Majesky MW, Schwartz SM, Pritzi P, Gordon K, Gown AM. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest. 1991 Mar;87(3):847–858.[PMC free article] [PubMed] [Google Scholar]
  • Johnson RJ, Alpers CE, Yoshimura A, Lombardi D, Pritzl P, Floege J, Schwartz SM. Renal injury from angiotensin II-mediated hypertension. Hypertension. 1992 May;19(5):464–474. [PubMed] [Google Scholar]
  • Alpers CE, Hudkins KL, Floege J, Johnson RJ. Human renal cortical interstitial cells with some features of smooth muscle cells participate in tubulointerstitial and crescentic glomerular injury. J Am Soc Nephrol. 1994 Aug;5(2):201–209. [PubMed] [Google Scholar]
  • Arciniegas E, Sutton AB, Allen TD, Schor AM. Transforming growth factor beta 1 promotes the differentiation of endothelial cells into smooth muscle-like cells in vitro. J Cell Sci. 1992 Oct;103(Pt 2):521–529. [PubMed] [Google Scholar]
  • Yamamoto T, Noble NA, Miller DE, Border WA. Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis. Kidney Int. 1994 Mar;45(3):916–927. [PubMed] [Google Scholar]
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033.
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033.
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Abstract
Interstitial fibrosis is a common outcome of longterm ureteral obstruction. One pathological arm of the fibrotic reaction in diverse tissue loci and experimental models is the retraction of granulation tissue. The role of the myofibroblast in granulation tissue contraction and fibrocontractive diseases has been well established, but the mechanisms leading to differentiation of fibroblastic cells into myofibroblasts during the evolution of inflammation are not yet fully clarified. Investigators using other model systems have shown that macrophage-derived transforming growth factor-beta 1 (TGF-beta 1) may be pivotal in the process of myofibroblast modulation. Our laboratory has shown that the unilateral ureteral obstruction in the rat is characterized by a 20-fold increment in infiltrating renal cortical interstitial macrophages, an increase in cortical TGF-beta 1 gene expression, which parallels the infiltrating macrophage burden, and immunolocalization of this peptide growth factor in close proximity to resident interstitial fibroblasts. Because of this model's features, it was our aim to assess whether a myofibroblastic modulation was operant in the renal cortex of obstructed rat kidneys versus the control contralateral unobstructed kidney specimens. Immunolabeling for alpha-smooth muscle actin and the intermediate filament protein, desmin, was detected and steadily intensified from 24 to 96 hours after unilateral ureteral obstruction in obstructed kidneys only. In temporal concert with the detection of alpha-smooth muscle actin protein, the mRNA expression for this cytoskeletal component exhibited 3.7-, 15.7-, and 4.1-fold increments in the renal cortex of obstructed kidneys versus the contralateral unobstructed kidney specimens at 24, 48, and 96 hours after unilateral ureteral obstruction, respectively. Whole body X-irradiation, administered to rats 11 days before proximal left ureteral ligation, significantly lowered cortical interstitial macrophage number, cortical TGF-beta and alpha-smooth muscle actin mRNA levels as well as the intensity of immunolabeling for alpha-smooth muscle actin from 12 to 96 hours after unilateral ureteral obstruction. These data support a postulate that renal cortical TGF-beta 1, derived from the infiltrating macrophage, in part, contributes to the subsequent interstitial fibrosis response to renal injury by fostering the modulation of fibroblasts to myofibroblasts within the renal cortex after ureteral obstruction.
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