scholarly journals Interaction of complement and clusterin in renal injury.

1992 ◽  
Vol 3 (5) ◽  
pp. 1172-1179
Author(s):  
R Correa-Rotter ◽  
T H Hostetter ◽  
K A Nath ◽  
J C Manivel ◽  
M E Rosenberg
Keyword(s):  
Folic Acid ◽  
Complement System ◽  
Renal Injury ◽  
Membrane Attack Complex ◽  
Cell Aggregation ◽  
Cytolytic Activity ◽  
Subtotal Nephrectomy ◽  
Renal Ablation ◽  
Clusterin Expression ◽  
Deficient Mice

Clusterin is a heterodimeric glycoprotein that has been associated with such diverse biologic functions as reproduction, cell regression, cell aggregation, and regulation of the cytolytic activity of the membrane attack complex of complement. Clusterin is a component of glomerular immune deposits in the kidney, and increased clusterin expression occurs in a number of renal injury states. To further explore the interaction between clusterin and complement, the requirement for an intact complement system for renal clusterin induction in an acute (folic acid nephropathy) and a chronic (subtotal renal ablation) model of renal injury was examined. After it was first demonstrated that folic acid increased renal clusterin mRNA in the rat, a species in which renal clusterin was highly inducible by other stimuli, the effects of folic acid (250 mg/kg ip) on clusterin mRNA and immunoreactivity were examined in mice sufficient and deficient for the fifth component of complement. Similar increases in clusterin mRNA and immunoreactivity were seen in both the C5-sufficient and C5-deficient mice compared with their respective vehicle-injected control groups. Renal clusterin mRNA was also increased to a similar extent in the remaining kidney of both C5-sufficient and C5-deficient mice 10 days after subtotal nephrectomy. In conclusion, the induction of clusterin after folic acid administration or subtotal nephrectomy was independent of the presence of an intact complement system, because similar increases in clusterin expression were observed in C5-sufficient and C5-deficient mice.

scholarly journals P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

2007 ◽  
Vol 72 (10) ◽  
pp. 1233-1241 ◽  
Author(s):  
M. Huls ◽  
C. Kramers ◽  
E.N. Levtchenko ◽  
M.J.G. Wilmer ◽  
H.B.P.M. Dijkman ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Renal Injury ◽  
P Glycoprotein ◽  
Ischemic Renal Injury ◽  
Deficient Mice

scholarly journals Osteogenic protein-1 mRNA expression is selectively modulated after acute ischemic renal injury.

1998 ◽  
Vol 9 (8) ◽  
pp. 1456-1463
Author(s):  
M M Almanzar ◽  
K S Frazier ◽  
P H Dube ◽  
A I Piqueras ◽  
W K Jones ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Renal Injury ◽  
Tissue Repair ◽  
Western Blots ◽  
Time Points ◽  
Mrna Content ◽  
Repair Mechanisms ◽  
Osteogenic Protein ◽  
Ischemic Renal Injury ◽  
Deficient Mice

Osteogenic protein-1 (OP-1) is a morphogenetic factor highly expressed in the kidney and involved in tissue repair and development. Homozygous OP-1-deficient mice die shortly after birth due mainly to arrest of renal growth and differentiation. Because postischemic injury involves several repair mechanisms, this study examined whether kidney OP-1 mRNA expression is modulated after ischemia. Acute ischemic renal injury was achieved in rats by unilateral clamping of the renal pedicle followed by reperfusion. Rats were killed at 3, 6, 12, 24, and 48 h and 7 d after reperfusion, and kidneys were microdissected and analyzed by histology and Northern and Western blots. Changes in OP-1 mRNA were determined by measuring the ratio of OP-1/glyceraldehyde 3-phosphate dehydrogenase signals for each OP-1 transcript (4.0 and 2.4 kb) from ischemic, opposite, and sham-operated rats. The OP-1 mRNA content for transcript 4.0 kb was fivefold lower in the whole ischemic kidney compared with that in sham animals 24 h after reperfusion. In the ischemic medulla, OP-1 mRNA was strikingly downregulated 20-fold when compared with the ischemic cortex. Results for transcript 2.4 kb and for the other time points were comparable. OP-1 mRNA expression was also affected in the opposite medulla compared with the sham medulla. However, only in the ischemic medulla was the relative OP-1 content significantly lower at all time points. Similar results were obtained when analyzing OP-1 protein by Western blot at 24 h after reperfusion. Seven days after reperfusion, the levels of OP-1 mRNA returned to baseline. In conclusion, kidney OP-1 mRNA and protein are selectively downregulated in the medulla after acute ischemic renal injury. OP-1 modulation may be a key element for kidney repair.

Abstract 153: Born with a Single Kidney versus Nephrectomy: Similar End Point, Different Mechanism of Injury

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Xuexiang Wang ◽  
Ashley Johnson ◽  
Jonathan Lee ◽  
Leah Solberg-Woods ◽  
Michael R Garrett
Keyword(s):  
Renal Function ◽  
Renal Injury ◽  
Time Course ◽  
Course Evaluation ◽  
Pathophysiological Mechanism ◽  
Mechanism Of Injury ◽  
Nephron Number ◽  
Unilateral Renal Agenesis ◽  
Renal Ablation ◽  
Single Kidney

A relatively common abnormality of the urogenital tract in humans is the development of only a single kidney (1:500 to 1:1000). Clinical studies suggest that patients born with a single kidney can develop proteinuria, hypertension, and even renal failure later in life. In contrast, studies in children who undergo nephrectomy or adults who serve as kidney donors appear to exhibit little difference in renal function compared to two-kidney subjects. Invasive techniques such as nephrectomy or renal ablation have been used to generate animal models to recapitulate this human congenital disorder. The progression of injury in these models is attributed to hyperfiltration which refers to changes in hemodynamics that cause glomerular damage leading to hypertension. Recently, our lab developed a new genetic animal model [heterogeneous stock derived model of unilateral renal agenesis, (HSRA)] that develops with a single kidney in 50-75% of offspring. The model is characterized by reduced nephron number, kidney hypertrophy, and renal injury that leads to a decline in renal function. Time course evaluation of blood pressure, renal hemodynamics, and renal injury was performed in 4 groups; (1) HSRA-S (1-kidney), (2) HSRA-C (2-kidney littermates), (3) HSRA-UNX3 (uninephrectomy-week 3) and (4) HSRA-UNX8 (uninephrectomy-week 8). Nephrectomized animals demonstrated hyperfiltration, whereas single kidney animals (HSRA-S) did not. This suggests a different pathophysiological mechanism of injury between congenital and nephrectomized rats. At later time points, proteinuria for HSRA-UNX3 (82±22.9 mg/24h) and HSRA-UNX8 (46±18.1) were significantly higher than HSRA-C (11±6.4), while HSRA-S (109±15.7) demonstrated the highest proteinuria. GFR was lowest in HSRA-S (656±123.9 ul/min/gKW), followed by HSRA-UNX3 (1151±112.4), HSRA-UNX8 (1309±98.3) and HSRA-C (1544±111.7). Microarray studies have identified several developmental genes ( Hox5b , Smoc2 and c- Kit ) that may be linked to reduced nephron number and other structural changes that could predispose the HSRA-S to kidney injury later in life. These results demonstrate that rats born with a single kidney are more prone to renal injury than nephrectomized rats and the mechanism is likely different.

scholarly journals Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex

1999 ◽  
Vol 277 (6) ◽  
pp. C1263-C1268 ◽  
Author(s):  
Constantinos Kyriakides ◽  
William Austen ◽  
Yong Wang ◽  
Joanne Favuzza ◽  
Lester Kobzik ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Membrane Attack Complex ◽  
Wild Type ◽  
Complement Components ◽  
Neutrophil Activity ◽  
Deficient Mice ◽  
Terminal Complement

The relative inflammatory roles of neutrophils, selectins, and terminal complement components are investigated in this study of skeletal muscle reperfusion injury. Mice underwent 2 h of hindlimb ischemia followed by 3 h of reperfusion. The role of neutrophils was defined by immunodepletion, which reduced injury by 38%, as did anti-selectin therapy with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin (Ig) fusion protein. Injury in C5-deficient and soluble complement receptor type 1-treated wild-type mice was 48% less than that of untreated wild-type animals. Injury was restored in C5-deficient mice reconstituted with wild-type serum, indicating the effector role of C5–9. Neutropenic C5-deficient animals showed additive reduction in injuries (71%), which was lower than C5-deficient neutrophil-replete mice, indicating neutrophil activity without C5a. Hindlimb histological injury was worse in ischemic wild-type and C5-deficient animals reconstituted with wild-type serum. In conclusion, the membrane attack complex and neutrophils act additively to mediate skeletal muscle reperfusion injury. Neutrophil activity is independent of C5a but is dependent on selectin-mediated adhesion.

scholarly journals RIPK3 blockade attenuates kidney fibrosis in a folic acid model of renal injury

2020 ◽  
Vol 34 (8) ◽  
pp. 10286-10298
Author(s):  
Ying Shi ◽  
Chunling Huang ◽  
Hao Yi ◽  
Qinghua Cao ◽  
Yongli Zhao ◽  
...  
Keyword(s):  
Folic Acid ◽  
Renal Injury ◽  
Kidney Fibrosis

Myeloperoxidase deficiency ameliorates progression of chronic kidney disease in mice

2014 ◽  
Vol 307 (4) ◽  
pp. F407-F417 ◽  
Author(s):  
Alexander Lehners ◽  
Sascha Lange ◽  
Gianina Niemann ◽  
Alva Rosendahl ◽  
Catherine Meyer-Schwesinger ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Matrix Metalloproteinase ◽  
Collagen Type ◽  
Matrix Metalloproteinase 2 ◽  
Marker Genes ◽  
Wild Type ◽  
Renal Ablation ◽  
The Impact ◽  
Deficient Mice

Myeloperoxidase (MPO) is an enzyme expressed in neutrophils and monocytes/macrophages. Beside its well-defined role in innate immune defence, it may also be responsible for tissue damage. To identify the role of MPO in the progression of chronic kidney disease (CKD), we investigated CKD in a model of renal ablation in MPO knockout and wild-type mice. CKD was induced by 5/6 nephrectomy. Mice were followed for 10 wk to evaluate the impact of MPO deficiency on renal morbidity. Renal ablation induced CKD in wild-type mice with increased plasma levels of MPO compared with controls. No difference was found between MPO-deficient and wild-type mice regarding albuminuria 1 wk after renal ablation, indicating similar acute responses to renal ablation. Over the next 10 wk, however, MPO-deficient mice developed significantly less albuminuria and glomerular injury than wild-type mice. This was accompanied by a significantly lower renal mRNA expression of the fibrosis marker genes plasminogen activator inhibitor-I, collagen type III, and collagen type IV as well as matrix metalloproteinase-2 and matrix metalloproteinase-9. MPO-deficient mice also developed less renal inflammation after renal ablation, as indicated by a lower infiltration of CD3-positive T cells and F4/80-positive monocytes/macrophages compared with wild-type mice. In vitro chemotaxis of monocyte/macrophages isolated from MPO-deficient mice was impaired compared with wild-type mice. No significant differences were observed for mortality and blood pressure after renal ablation. In conclusion, these results demonstrate that MPO deficiency ameliorates renal injury in the renal ablation model of CKD in mice.

Dynamic Expression of the Membrane Attack Complex (MAC) of the Complement System in Failing Human Myocardium

2006 ◽  
Vol 97 (11) ◽  
pp. 1626-1629 ◽  
Author(s):  
Guilherme H.M. Oliveira ◽  
Corinne N. Brann ◽  
Katy Becker ◽  
Vinay Thohan ◽  
Michael M. Koerner ◽  
...  
Keyword(s):  
Complement System ◽  
Membrane Attack Complex ◽  
Human Myocardium ◽  
Dynamic Expression ◽  
The Complement System

scholarly journals Immunity against the Obligate Intracellular Bacterial PathogenRickettsia australisRequires a Functional Complement System

2018 ◽  
Vol 86 (6) ◽  
Author(s):  
Sean P. Riley ◽  
Abigail I. Fish ◽  
Fabio Del Piero ◽  
Juan J. Martinez
Keyword(s):  
Complement System ◽  
Membrane Attack Complex ◽  
Immune Functions ◽  
Complement Protein ◽  
Membrane Pore ◽  
Content Type ◽  
Genetic Ablation ◽  
Obligate Intracellular ◽  
Susceptibility To Infection ◽  
The Complement System

ABSTRACTThe complement system has a well-defined role in deterring blood-borne infections. However, complement is not entirely efficacious, as several bacterial pathogens, including some obligate intracellular pathogens, have evolved mechanisms for resistance. It is presumed that obligate intracellular bacteria evade complement attack by residing within a host cell; however, recent studies have challenged this presumption. Here, we demonstrate that the complement system is activated during infection with the obligate intracellular bacteriumRickettsia australisand that genetic ablation of complement increases susceptibility to infection. Interaction ofRickettsia australiswith serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influenceR. australis.The C9-dependent membrane attack complex can lead to deposition of a bacteriolytic membrane pore on the bacteria, but this system does not contribute to control of rickettsial infection. Similarly, complement receptor (CR1/2)-dependent opsonophagocytosis may lead to engulfment and killing of the bacteria, but this system is also dispensable for immunity. Nevertheless, intact complement is essential for naturally acquired and antibody-mediated immunity toRickettsiainfection. Comparison of infection in mice lacking the central complement protein C3 with infection in their wild-type counterparts demonstrated decreases in gamma interferon (IFN-γ) production, IgG secretion, and spleen hyperplasia in animals lacking complement. The correlation between loss of secondary immune functions and loss of complement indicates that the proinflammatory signaling components of the complement system, and not membrane attack complex or opsonophagocytosis, contribute to the immune response to this pathogen.

Sign in / Sign up

Export Citation Format

Share Document