Blood coagulation in glomerulonephritis

Belovezhdov, N; Robeva, R; Genova, Ventsislava Pencheva

doi:10.1007/bf02082608

Cited by 2 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although Gas6 inhibition is beneficial in glomerulonephritis, chronic Gas6 inhibition might cause bleeding and anemia by inhibiting platelet aggregation [31]. Previous evidence showed that the coagulation cascade is activated in severe human and experimental glomerulonephritis [15] made it unclear whether Gas6 deletion ameliorated glomerulonephritis through Axl-independent suppression of coagulation or through an Axl-dependent anti-inflammatory effect. Although our data do not eliminate the possibility that the anti-thrombotic activity of Gas6 inhibition contributes to its beneficial effects in nephritis, our studies with Axl-deficient mice and R428-treated mice demonstrate that Gas6 activation of Axl is an important mechanism by which it contributes to the pathogenesis of glomerular disease.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of Gas6 protects mice against mesangial cell proliferation and glomerular hypertrophy and improves proteinuria and survival in anti-Thy1.1-induced rat nephritis [12]. However, because Gas6 is an important coagulation factor and the coagulation cascade is activated in severe human and experimental nephritis [15], it is unclear whether Gas6 deletion ameliorates nephritis by TAM-independent suppression of coagulation or by a TAM-dependent anti-inflammatory effect. Therefore, targeting Axl offers a clearer mechanism of action and a potentially safer approach than targeting Gas6 to suppress nephritis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis

Zhen

Lee

Finkelman

et al. 2018

Journal of Autoimmunity

View full text Add to dashboard Cite

Glomerulonephritis (GN) is a typical lesion in autoantibody and immune complex disorders, including SLE. Because the Gas6/Axl pathway has been implicated in the pathogenesis of many types of GN, targeting this pathway might ameliorate GN. Consequently, we have studied the efficacy and mechanism of R428, a potent selective Axl inhibitor, in the prevention of experimental anti-GBM nephritis. Axl upregulation was investigated with Sp1/3 siRNA in the SV40-transformed mesangial cells. For Axl inhibition, a daily dose of R428 (125 mg/kg) or vehicle was administered orally. GN was induced with anti-GBM sera. Renal disease development was followed by serial blood urine nitrogen (BUN) determinations and by evaluation of kidney histology at the time of sacrifice. Axl-associated signaling proteins were analyzed by Western blotting and inflammatory cytokine secretion was analyzed by Proteome array. SiRNA data revealed the transcription factor Sp1 to be an important regulator of mesangial Axl expression. Anti-GBM serum induced severe nephritis with azotemia, protein casts and necrotic cell death. R428 treatment diminished renal Axl expression and improved kidney function, with significantly decreased BUN and glomerular proliferation. R428 treatment inhibited Axl and significantly decreased Akt phosphorylation and renal inflammatory cytokine and chemokine expression; similar effects were observed in anti-GBM antiserum-treated Axl-KO mice. These studies support a role for Axl inhibition in glomerulonephritis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis

Zhen

Lee

Finkelman

et al. 2018

Journal of Autoimmunity

View full text Add to dashboard Cite

show abstract

Platelet function in disseminated intravascular coagulation: A systematic review

2018

View full text Add to dashboard Cite

Disseminated intravascular coagulation (DIC) has a well-examined pathophysiology, yet some essential elements remain undetermined. During DIC, platelets play an important role in the development of micro thrombosis, but changes in platelet function parameters and their association with development of DIC have not been established. The present systematic review investigated reported associations between platelet function (activation, aggregation, and adhesion) and DIC. We performed a literature search in Embase and PubMed, following the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines. In total, 22 articles were included; 14 human studies, seven animal studies, and one with both human and animal subjects. Platelet activation markers were generally reported to be higher in both DIC patients and animals with DIC than healthy controls, and higher among patients with DIC than patients without DIC. Six human and six animal studies investigated platelet aggregation, which were overall reported to be lower in DIC than in non-DIC or in healthy controls in both human and animal studies. Platelet aggregation was deemed to be confounded by low platelet counts, which are known to affect platelet aggregation analyses even within the reference interval. In conclusion, platelet activation analyses showed promise in diagnosis of DIC, but semi-automatization and standardization are warranted before these can be implemented in daily clinical practice. Changes in platelet aggregation analyses during DIC remain inconclusive, and further studies including adjustment for low platelet count are needed to clarify the role of platelet aggregation in DIC.

show abstract

Blood coagulation in glomerulonephritis

Cited by 2 publications

References 12 publications

Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis

Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis

Platelet function in disseminated intravascular coagulation: A systematic review

Contact Info

Product

Resources

About