The Experts below are selected from a list of 6621 Experts worldwide ranked by ideXlab platform
Richard J. Johnson - One of the best experts on this subject based on the ideXlab platform.
-
ckd of unknown origin in central america the case for a mesoamerican nephropathy
American Journal of Kidney Diseases, 2014Co-Authors: Ricardo Correarotter, Catharina Wesseling, Richard J. JohnsonAbstract:An epidemic of chronic kidney Disease of unknown origin has emerged in the last decade in Central America and has been named Mesoamerican nephropathy. This form of chronic kidney Disease is present primarily in young male agricultural workers from communities along the Pacific coast, especially workers in the sugarcane fields. In general, these men have a history of manual labor under very hot conditions in agricultural fields. Clinically, they usually present with normal or mildly elevated systemic blood pressure, asymptomatic yet progressive reduction in estimated glomerular filtration rate, low-grade non-nephrotic proteinuria, and often hyperuricemia and or hypokalemia. Diabetes is absent in this population. Kidney biopsies that have been performed show a chronic Tubulointerstitial Disease with associated secondary glomerulosclerosis and some signs of glomerular ischemia. The cause of the Disease is unknown; this article discusses and analyzes some of the etiologic possibilities currently under consideration. It is relevant to highlight that recurrent dehydration is suggested in multiple studies, a condition that possibly could be exacerbated in some cases by other conditions, including the use of nonsteroidal anti-inflammatory agents. At present, Mesoamerican nephropathy is a medical enigma yet to be solved.
-
Tubulointerstitial Disease role of ischemia and microvascular Disease
Current Opinion in Nephrology and Hypertension, 2003Co-Authors: Takahiko Nakagawa, Dukhee Kang, Ryuji Ohashi, Shinichi Suga, Jaime Herreraacosta, Bernardo Rodrigueziturbe, Richard J. JohnsonAbstract:Purpose of review Tubulointerstitial injury is characteristic of aging-associated renal injury and progressive renal Disease. Salt-sensitive hypertension is also associated with Tubulointerstitial inflammation, especially when accompanied by microvascular Disease. Here we summarize recent studies on the pathogenesis and consequences of Tubulointerstitial Disease, emphasizing the role of ischemia and the microvasculature. Recent findings Tubulointerstitial injury occurs via several mechanisms of which one of the most important is chronic ischemia. Recent studies suggest that chronic vasoconstriction may contribute to the renal injury associated with angiotensin II, catecholamines, nitric oxide inhibition, hypokalemia, hyperuricemia, and cyclosporine nephropathy. Salt-sensitivity may result as a consequence of the Tubulointerstitial inflammatory response to these conditions, and this appears to be perpetuated by the development of preglomerular vascular Disease. With progression of Tubulointerstitial Disease there is also a loss of peritubular capillaries, and stimulating microvascular growth with angiogenic factors can stabilize renal function in these models. Summary Ischemia secondary to vasoconstriction or to structural changes of the renal vasculature may have important consequences both in terms of mediating salt-sensitive hypertension and renal progression. Angiogenic factors may have potential benefit in preventing or treating these conditions.
-
hypertension a microvascular and Tubulointerstitial Disease
Journal of Hypertension, 2002Co-Authors: Richard J. Johnson, Bernardo Rodrigueziturbe, George F Schreiner, Jaime HerreraacostaAbstract:The vast majority of patients with essential hypertension have structural changes in their kidneys consisting of preglomerular vascular Disease ('arteriolosclerosis') and Tubulointerstitial injury. Most authorities have assumed that these structural changes occur secondary to hypertensive renal injury. However, Goldblatt proposed that primary renal microvascular Disease might be the cause of some forms of hypertension. In this paper we present recent studies from our group that support a role for both preglomerular vascular Disease as well as the Tubulointerstitial inflammatory response in mediating salt-sensitivity. We propose that subtle acquired renal injury may underlie the etiology of some forms of salt-sensitive hypertension.
-
role of fas cd95 in Tubulointerstitial Disease induced by unilateral ureteric obstruction
American Journal of Physiology-renal Physiology, 1999Co-Authors: Jeremy Hughes, Richard J. JohnsonAbstract:Murine renal tubular epithelial cells and interstitial fibroblasts may express both Fas (CD95) death receptor and Fas ligand and are vulnerable to Fas-mediated death in vitro. We therefore hypothes...
-
reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension cardiovascular Disease and renal Disease
American Journal of Kidney Diseases, 1999Co-Authors: Richard J. Johnson, Shinichi Suga, Salah Kivlighn, Yoongoo Kim, Agnes B FogoAbstract:An elevated uric acid level is associated with cardiovascular Disease. Hyperuricemia is predictive for the development of both hypertension and coronary artery Disease; it is increased in patients with hypertension, and, when present in hypertension, an elevated uric acid level is associated with increased cardiovascular morbidity and mortality. Serum uric acid level should be measured in patients at risk for coronary artery Disease because it carries prognostic information. Hyperuricemia is caused by decreased renal excretion. In this article, we suggest that this may be mediated by intrarenal ischemia with lactate generation and the inhibition of the secretion of urate by the anion-exchange transport system. The possibility that hyperuricemia directly contributes to cardiovascular or renal Disease needs to be reconsidered. Although hyperuricemia is associated with a number of cardiovascular or renal risk factors, several studies have found uric acid level to be independently associated with increased mortality by multivariate analysis. If hyperuricemia is directly toxic, the most likely site is the kidney. Chronic hyperuricemia is strongly associated with chronic Tubulointerstitial Disease, and many of these patients have decreased renal function. Although it is possible that the hyperuricemia could simply be the consequence of the renal Disease, further studies are necessary to rule out a pathogenic role for uric acid in the development of renal Disease and salt-dependent hypertension.
Raimund Pichler - One of the best experts on this subject based on the ideXlab platform.
-
obstructive uropathy in the mouse role of osteopontin in interstitial fibrosis and apoptosis
Kidney International, 1999Co-Authors: Katherine L Gordon, Raimund Pichler, Cecilia M Giachelli, Jeremy Hughes, Vuddhidej OphascharoensukAbstract:Obstructive uropathy in the mouse: Role of osteopontin in interstitial fibrosis and apoptosis. Background Osteopontin is a macrophage adhesive protein that is expressed by renal tubules in Tubulointerstitial Disease. Methods To investigate the function of OPN, we induced Tubulointerstitial Disease in OPN null mutant (OPN -/- ) and wild-type (OPN +/+ ) mice by unilateral ureteral ligation. Tissue was analyzed for macrophages (ED-1), types I and IV collagen deposition, TGF-βbgr; expression, and for tubular and interstitial cell apoptosis. Results Obstructed kidneys from both OPN -/- and OPN +/+ mice developed hydronephrosis, tubular atrophy, interstitial inflammation and fibrosis. OPN was absent in OPN -/- kidneys but was increased in obstructed OPN +/+ kidneys. Macrophage influx, measured by computer-assisted quantitative immunostaining, was less in OPN -/- mice compared to OPN +/+ mice at day 4 (threefold, P P -/- kidneys ( P in situ hybridization) and a near significant 34% reduction in cortical TGF-βbgr; activity ( P = 0.06) compared to obstructed OPN +/+ kidneys at day 14. Obstructed kidneys from OPN -/- mice also had more interstitial and tubular apoptotic cells (TUNEL assay) compared to obstructed OPN +/+ mice at all time points. The ability of OPN to act as a cell survival factor was also documented by showing that the apoptosis of serum-starved NRK52E renal epithelial cells was markedly enhanced in the presence of neutralizing anti-OPN antibody. Conclusion OPN mediates early interstitial macrophage influx and interstitial fibrosis in unilateral ureteral obstruction. OPN may also function as a survival factor for renal Tubulointerstitial cells.
-
Thrombospondin 1 precedes and predicts the development of Tubulointerstitial fibrosis in glomerular Disease in the rat
Kidney international, 1998Co-Authors: C Hugo, Stuart J. Shankland, Raimund Pichler, William G. Couser, Richard J. JohnsonAbstract:Thrombospondin 1 precedes and predicts the development of Tubulointerstitial fibrosis in glomerular Disease in the rat. Tubulointerstitial fibrosis is one of the most important histologic features that predicts progression in kidney Disease. Thrombospondin 1 is an extracellular matrix protein that can activate latent TGF- β , a cytokine implicated in the pathogenesis of Tubulointerstitial fibrosis. We examined the expression of thrombospondin 1 in several animal models of glomerulonephritis (anti-Thy1 model, aminonucleoside nephrosis, passive Heymann nephritis) that are associated with Tubulointerstitial Disease. Thrombospondin 1 mRNA and protein were transiently increased in tubular cells, myofibroblasts and some macrophages in areas of Tubulointerstitial injury. Thrombospondin 1 expression always preceded the development of Tubulointerstitial fibrosis, and correlated quantitatively and spatially with the later development of interstitial fibrosis. Thrombospondin 1 expression predicted the severity of Tubulointerstitial fibrosis better than the degree of macrophage or myofibroblast accumulation. Thrombospondin 1 expression was associated with increased expression and activation of TGF- β 1 and decreased expression of LAP-TGF- β in areas of Tubulointerstitial injury. We conclude that thrombospondin 1 is an early marker predicting the development of Tubulointerstitial kidney Disease. De novo expression of thrombospondin 1 is associated and colocalized with increased expression of TGF- β 1 and decreased expression of LAP-TGF- β during the development of Tubulointerstitial Disease in vivo . These data are consistent with the possibility that thrombospondin 1 may be an endogenous activator of TGF- β .
-
the pathogenesis of Tubulointerstitial Disease associated with glomerulonephritis the glomerular cytokine theory
Mineral and Electrolyte Metabolism, 1995Co-Authors: Raimund Pichler, William G. Couser, Cecilia M Giachelli, Bessie A Young, Charles E Alpers, Richard J. JohnsonAbstract:Numerous studies have suggested that Tubulointerstitial Disease has a major impact on the overall function and prognosis of glomerular Disease. The mechanism by which Tubulointerstitial Disease develops in patients with glomerular and other Diseases is unknown. In this review, we discuss the hypothesis that factors released from injured glomeruli act on tubules and interstitial cells to induce expression of chemotactic and adhesive factors that attract mononuclear cells into the interstitium. Evidence is provided that osteopontin is one candidate leukocyte adhesive factor involved in this process, but others are likely involved. The recruited leukocytes (primarily macrophages) then release inflammatory mediators that injure tubular cells and activate interstitial fibroblasts, resulting in Tubulointerstitial injury with eventual fibrosis.
-
Tubulointerstitial Disease in glomerulonephritis potential role of osteopontin uropontin
American Journal of Pathology, 1994Co-Authors: Raimund Pichler, Katherine L Gordon, Cecilia M Giachelli, Charles E Alpers, Jeffrey W Pippin, Donna Lombardi, Stephen M Schwartz, Richard J. JohnsonAbstract:Abstract Interstitial inflammation and tubular injury accompany most types of glomerulonephritis and are likely to mediate progressive renal injury. We hypothesized that the interstitial monocyte/macrophage accumulation in nephritis involves osteopontin, a cell attachment glycoprotein that avidly binds macrophages in vitro and induces a macrophage-rich infiltrate on subcutaneous injection in mice (Singh et al, J Exp Med, 1990, 171: 1931). In this study, we demonstrate that osteopontin messenger RNA and protein levels are up-regulated in a proportion of proximal and distal tubules in three experimental models of glomerulonephritis. In all three models, the expression of osteopontin initially precedes histological evidence of tubular injury, but is correlated with subsequent sites of monocyte/macrophage accumulation and tubular damage. Osteopontin expression also correlates with the severity of the Tubulointerstitial injury, being greatest in amino-nucleoside nephrosis. These data suggest that 1) osteopontin is up-regulated in tubules in glomerular Disease; 2) osteopontin may be important for macrophage accumulation at specific sites in Diseased tissue; and 3) osteopontin may therefore have a role in the pathogenesis of the Tubulointerstitial injury that accompanies glomerulonephritis.
Mark A Perazella - One of the best experts on this subject based on the ideXlab platform.
-
the challenges of acute interstitial nephritis time to standardize
Kidney, 2021Co-Authors: Dennis G Moledina, Mark A PerazellaAbstract:Acute interstitial nephritis (AIN) is a well-known cause of acute kidney Disease (AKD) and CKD and is associated with progression to ESKD (1⇓⇓⇓⇓–6). Accordingly, it represents an important problem for clinicians caring for these patients. AIN is primarily an immune-mediated kidney injury triggered by use of certain medications, in particular antibiotics, PPIs, NSAIDs, and immune checkpoint inhibitors (ICPIs), or by autoimmune Diseases, such as Sjogren syndrome, sarcoidosis, IgG4-related Tubulointerstitial Disease, and TINU. In developed countries, medications are the most common cause of AIN (>70%), whereas the number approximates 50% in developing countries. Infectious agents are a less common cause of AIN, except in developing countries. The overall incidence of AIN in kidney biopsy registries is 2%–5%, whereas AIN is observed in approximately 15%–20% of patients with AKI or AKD who undergo kidney biopsy (1⇓–3). The actual number is likely higher as many patients with AKI/AKD do not undergo biopsy and are presumed to have acute tubular injury (ATI). Importantly, diagnosing AIN clinically is often quite challenging, making kidney biopsy a frequent requirement to definitively confirm the diagnosis and guide therapy (Figure 1). Furthermore, delayed or missed AIN diagnosis leads to ongoing inflammation with resulting interstitial fibrosis, tubular atrophy, and permanent kidney damage, which may be the explanation for CKD occurring in 40%–60% of patients after an episode of AIN (4,5). Approximately 2% of CKD is considered to be due to AIN, which is equivalent to 10 million prevalent worldwide cases. Furthermore, AIN is the primary cause of ESKD in 3%–4% of incident patients (6). It is one of the few potentially treatable causes of AKI if identified and treated early. In view of these data, three key challenges that limit the diagnosis and management of patients suspected of having …
-
clinical approach to diagnosing acute and chronic Tubulointerstitial Disease
Advances in Chronic Kidney Disease, 2017Co-Authors: Mark A PerazellaAbstract:Tubulointerstitial Diseases are a relatively common cause of acute and/or chronic kidney Disease. Acute Tubulointerstitial nephritis (ATIN) most commonly develops in patients exposed to various medications; however, it can occur from infections, autoimmune and systemic Diseases, environmental exposures, and some idiopathic causes. Chronic Tubulointerstitial nephritis may develop in patients with previous ATIN or may be the initial manifestation of an autoimmune, systemic, environmental, or metabolic process. It can be challenging for clinicians to differentiate the various causes of acute and chronic kidney Disease. In particular, distinguishing ATIN from other causes of acute kidney injury, such as acute tubular necrosis or a rapidly progressive glomerulonephritis, is important as treatment and prognosis are often quite different. To this end, clinicians use clinical assessment, certain laboratory data, and various imaging tests to make a diagnosis. Unfortunately, most of these tests are insufficient for this purpose. As a result, kidney biopsy is often required to accurately diagnose ATIN and guide management. For chronic Tubulointerstitial nephritis, kidney biopsy is needed less often as available therapies for this entity, with a few exceptions, are limited and primarily supportive.
-
drug induced renal failure a focus on Tubulointerstitial Disease
Clinica Chimica Acta, 2005Co-Authors: Glen S Markowitz, Mark A PerazellaAbstract:Therapeutic agents induce acute renal failure (ARF) by promoting various types of injury to the kidney. Acute interstitial nephritis (AIN) develops from medications that incite an allergic reaction, leading to interstitial inflammation and tubular damage. Acute tubular necrosis (ATN) is a dose-dependent process that develops from direct toxicity on tubular epithelia, typically in the absence of inflammation. Additional, less common patterns of drug-induced renal injury include osmotic nephropathy, crystal nephropathy, and acute nephrocalcinosis. This review focuses on the multitude of patterns of drug-induced renal failure due to Tubulointerstitial Disease.
Katherine L Gordon - One of the best experts on this subject based on the ideXlab platform.
-
obstructive uropathy in the mouse role of osteopontin in interstitial fibrosis and apoptosis
Kidney International, 1999Co-Authors: Katherine L Gordon, Raimund Pichler, Cecilia M Giachelli, Jeremy Hughes, Vuddhidej OphascharoensukAbstract:Obstructive uropathy in the mouse: Role of osteopontin in interstitial fibrosis and apoptosis. Background Osteopontin is a macrophage adhesive protein that is expressed by renal tubules in Tubulointerstitial Disease. Methods To investigate the function of OPN, we induced Tubulointerstitial Disease in OPN null mutant (OPN -/- ) and wild-type (OPN +/+ ) mice by unilateral ureteral ligation. Tissue was analyzed for macrophages (ED-1), types I and IV collagen deposition, TGF-βbgr; expression, and for tubular and interstitial cell apoptosis. Results Obstructed kidneys from both OPN -/- and OPN +/+ mice developed hydronephrosis, tubular atrophy, interstitial inflammation and fibrosis. OPN was absent in OPN -/- kidneys but was increased in obstructed OPN +/+ kidneys. Macrophage influx, measured by computer-assisted quantitative immunostaining, was less in OPN -/- mice compared to OPN +/+ mice at day 4 (threefold, P P -/- kidneys ( P in situ hybridization) and a near significant 34% reduction in cortical TGF-βbgr; activity ( P = 0.06) compared to obstructed OPN +/+ kidneys at day 14. Obstructed kidneys from OPN -/- mice also had more interstitial and tubular apoptotic cells (TUNEL assay) compared to obstructed OPN +/+ mice at all time points. The ability of OPN to act as a cell survival factor was also documented by showing that the apoptosis of serum-starved NRK52E renal epithelial cells was markedly enhanced in the presence of neutralizing anti-OPN antibody. Conclusion OPN mediates early interstitial macrophage influx and interstitial fibrosis in unilateral ureteral obstruction. OPN may also function as a survival factor for renal Tubulointerstitial cells.
-
Tubulointerstitial Disease in aging evidence for underlying peritubular capillary damage a potential role for renal ischemia
Journal of The American Society of Nephrology, 1998Co-Authors: Susan E Thomas, Terry T Oyama, Katherine L Gordon, Sharon Anderson, Stuart J. Shankland, Richard J. JohnsonAbstract:Aging is associated with a progressive decline in renal function and the development of glomerulosclerosis and interstitial fibrosis. Although many studies have addressed the cellular mechanisms of age-related glomerulosclerosis, less is known about the Tubulointerstitial fibrosis. In this study, aging (24 mo) rats develop Tubulointerstitial fibrosis characterized by tubular injury and focal tubular cell proliferation, myofibroblast activation, macrophage infiltration with increased immunostaining for the adhesive proteins osteopontin and intercellular adhesion molecule-1, and collagen IV deposition. Aging rats demonstrated immunostaining for endothelial nitric oxide synthase (eNOSIII) in renal tubular epithelial cells and infiltrating mononuclear cells in areas of Tubulointerstitial injury, with a relative loss of staining of the peritubular capillaries compared with young rats. The aging rats also displayed focal loss of peritubular capillaries (as noted by focally decreased RECA-1 and OX-2 staining) in areas of Tubulointerstitial injury. The areas of fibrosis and hypocellularity were associated with increased apoptosis of tubular and interstitial cells compared with young (3 mo) rats (25.4 +/- 5.3 versus 3.5 +/- 2.5 TUNEL-positive cells/0.25 mm2 in old versus young rats, P = 0.0001). It is concluded that Tubulointerstitial fibrosis in aging is an active process associated with interstitial inflammation and fibroblast activation. The progressive loss of cells in areas of fibrosis may be due to accelerated apoptosis. Furthermore, the Tubulointerstitial injury may be the consequence of ischemia secondary to peritubular capillary injury and altered eNOS expression.
-
Tubulointerstitial Disease in glomerulonephritis potential role of osteopontin uropontin
American Journal of Pathology, 1994Co-Authors: Raimund Pichler, Katherine L Gordon, Cecilia M Giachelli, Charles E Alpers, Jeffrey W Pippin, Donna Lombardi, Stephen M Schwartz, Richard J. JohnsonAbstract:Abstract Interstitial inflammation and tubular injury accompany most types of glomerulonephritis and are likely to mediate progressive renal injury. We hypothesized that the interstitial monocyte/macrophage accumulation in nephritis involves osteopontin, a cell attachment glycoprotein that avidly binds macrophages in vitro and induces a macrophage-rich infiltrate on subcutaneous injection in mice (Singh et al, J Exp Med, 1990, 171: 1931). In this study, we demonstrate that osteopontin messenger RNA and protein levels are up-regulated in a proportion of proximal and distal tubules in three experimental models of glomerulonephritis. In all three models, the expression of osteopontin initially precedes histological evidence of tubular injury, but is correlated with subsequent sites of monocyte/macrophage accumulation and tubular damage. Osteopontin expression also correlates with the severity of the Tubulointerstitial injury, being greatest in amino-nucleoside nephrosis. These data suggest that 1) osteopontin is up-regulated in tubules in glomerular Disease; 2) osteopontin may be important for macrophage accumulation at specific sites in Diseased tissue; and 3) osteopontin may therefore have a role in the pathogenesis of the Tubulointerstitial injury that accompanies glomerulonephritis.
William G. Couser - One of the best experts on this subject based on the ideXlab platform.
-
c5b 9 does not mediate chronic Tubulointerstitial Disease in the absence of proteinuria
Kidney International, 2005Co-Authors: Gopala K Rangan, William G. Couser, Jeffrey W Pippin, Jason D CoombesAbstract:C5b-9 does not mediate chronic Tubulointerstitial Disease in the absence of proteinuria . Background In nephrotic glomerular Diseases, the intratubular assembly of the membrane attack complex (C5b-9) is one of the principal mediators of chronic Tubulointerstitial damage. Here, we examined whether C5b-9 has a pathogenic role in Tubulointerstitial Disease in the absence of proteinuria. Methods Three pathophysiologically distinct models of nonproteinuric chronic Tubulointerstitial Disease were induced in Piebald-Viral-Glaxo (PVG) rats, with or without C6 deficiency (C6+ and C6): ( 1 ) unilateral ureteric obstruction (UUO, days 1, 3, 6, 14, and 21; N = 5–6/group); ( 2 ) cyclosporine (CsA) nephropathy (15 mg/kg SC daily with 0.05% sodium diet; day 14, 35 N = 9/group); and ( 3 ) streptozotocin (STZ)-induced diabetes (day 90, N = 8/group). Results The peritubular deposition of C5b-9 increased in all three models. In UUO, the number of vimentin-positive tubules, interstitial volume expansion, and monocyte accumulation were similar in both the C6+ and C6- groups at all time points. There was a trend toward an earlier peak in myofibroblast accumulation in C6- rats with UUO (d3 vs. d6; P = 0.05), but this did not prevent fibrosis at later time points. In CsA nephropathy, cortical Tubulointerstitial damage was also similar in both C6+ and C6- groups on day 14, despite equivalent CsA trough levels. Finally, in STZ-induced diabetes, rats did not develop proteinuria, and Tubulointerstitial Disease (distal tubule glycogen nephrosis, interstitial volume expansion, and tubular dilatation) was not altered by C6 deficiency. Conclusion These data suggest that, in contrast to proteinuric states, C5b-9 does not have a significant impact on the progression of Tubulointerstitial damage in nonproteinuric chronic renal Disease.
-
Thrombospondin 1 precedes and predicts the development of Tubulointerstitial fibrosis in glomerular Disease in the rat
Kidney international, 1998Co-Authors: C Hugo, Stuart J. Shankland, Raimund Pichler, William G. Couser, Richard J. JohnsonAbstract:Thrombospondin 1 precedes and predicts the development of Tubulointerstitial fibrosis in glomerular Disease in the rat. Tubulointerstitial fibrosis is one of the most important histologic features that predicts progression in kidney Disease. Thrombospondin 1 is an extracellular matrix protein that can activate latent TGF- β , a cytokine implicated in the pathogenesis of Tubulointerstitial fibrosis. We examined the expression of thrombospondin 1 in several animal models of glomerulonephritis (anti-Thy1 model, aminonucleoside nephrosis, passive Heymann nephritis) that are associated with Tubulointerstitial Disease. Thrombospondin 1 mRNA and protein were transiently increased in tubular cells, myofibroblasts and some macrophages in areas of Tubulointerstitial injury. Thrombospondin 1 expression always preceded the development of Tubulointerstitial fibrosis, and correlated quantitatively and spatially with the later development of interstitial fibrosis. Thrombospondin 1 expression predicted the severity of Tubulointerstitial fibrosis better than the degree of macrophage or myofibroblast accumulation. Thrombospondin 1 expression was associated with increased expression and activation of TGF- β 1 and decreased expression of LAP-TGF- β in areas of Tubulointerstitial injury. We conclude that thrombospondin 1 is an early marker predicting the development of Tubulointerstitial kidney Disease. De novo expression of thrombospondin 1 is associated and colocalized with increased expression of TGF- β 1 and decreased expression of LAP-TGF- β during the development of Tubulointerstitial Disease in vivo . These data are consistent with the possibility that thrombospondin 1 may be an endogenous activator of TGF- β .
-
the pathogenesis of Tubulointerstitial Disease associated with glomerulonephritis the glomerular cytokine theory
Mineral and Electrolyte Metabolism, 1995Co-Authors: Raimund Pichler, William G. Couser, Cecilia M Giachelli, Bessie A Young, Charles E Alpers, Richard J. JohnsonAbstract:Numerous studies have suggested that Tubulointerstitial Disease has a major impact on the overall function and prognosis of glomerular Disease. The mechanism by which Tubulointerstitial Disease develops in patients with glomerular and other Diseases is unknown. In this review, we discuss the hypothesis that factors released from injured glomeruli act on tubules and interstitial cells to induce expression of chemotactic and adhesive factors that attract mononuclear cells into the interstitium. Evidence is provided that osteopontin is one candidate leukocyte adhesive factor involved in this process, but others are likely involved. The recruited leukocytes (primarily macrophages) then release inflammatory mediators that injure tubular cells and activate interstitial fibroblasts, resulting in Tubulointerstitial injury with eventual fibrosis.
