Aliskiren Regulates Neonatal Fc Receptor and IgG Metabolism with Attenuation of Anti-GBM Glomerulonephritis in Mice

Kang, Ju Hyung; Baik, Haing Woon; Yoo, Seung Min; Kim, Joo Heon; Cheong, Hae Il; Park, Chung Gyu; Kang, Hee Gyung; Ha, Il Soo

doi:10.1159/000448789

Cited by 3 publications

(1 citation statement)

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“…The possibility that the beneficial effects of renin–angiotensin inhibition are mediated to some degree through the FcRn has also been investigated in the literature. In particular, treatment of a mice anti-GBM model of glomerulonephritis with the direct renin inhibitor Aliskeren (70) reduced the glomerular deposition of IgG and reduced proteinuria in parallel with elevations in circulating IgG levels. In fact, animals that do not harbor the FcRn do not develop proteinuria and have reduced deposition of IgG compared to wild-type animals when anti-GBM nephritis is induced.…”

Section: β2m Physiology and Pathophysiologymentioning

confidence: 99%

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

et al. 2017

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There is currently an unmet need for better biomarkers across the spectrum of renal diseases. In this paper, we revisit the role of beta-2 microglobulin (β2M) as a biomarker in patients with chronic kidney disease and end-stage renal disease. Prior to reviewing the numerous clinical studies in the area, we describe the basic biology of β2M, focusing in particular on its role in maintaining the serum albumin levels and reclaiming the albumin in tubular fluid through the actions of the neonatal Fc receptor. Disorders of abnormal β2M function arise as a result of altered binding of β2M to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of β2M as a predictor of renal function and clinical outcomes in recent large database studies against predictions made by recently developed whole body population kinetic models. Furthermore, we discuss recent animal data suggesting that contrary to textbook dogma urinary β2M may be a marker for glomerular rather than tubular pathology. We review the existing literature about β2M as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that β2M is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of β2M as a biomarker in a number of non-renal diseases. The goal of this comprehensive review is to direct attention to the multifaceted role of β2M as a biomarker, and its exciting biology in order to propose the next steps required to bring this recently rediscovered biomarker into the twenty-first century.

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Section: β2m Physiology and Pathophysiologymentioning

confidence: 99%

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

et al. 2017

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“Ways in which the neonatal Fc-receptor is involved in autoimmunity”

Lamamy

Boulard

Brachet³

et al. 2021

Journal of Translational Autoimmunity

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(Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis

Urushihara

Kondo

Kinoshita

et al. 2020

American Journal of Physiology-Renal Physiology

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(Pro)renin receptor ((P)RR) has multiple functions, but its regulation and role in the pathogenesis in glomerulonephritis (GN) are poorly defined. The aims of this study were to determine the effects of direct renin inhibition (DRI) and demonstrate the role of (P)RR on the progression of crescentic GN. Anti-glomerular basement membrane (GBM) nephritis rat model developed progressive proteinuria (83.64 ± 10.49 mg/day) and glomerular crescent formation (% glomerular crescent: 62.1 ± 2.3%), accompanied by increased macrophage infiltration and glomerular expression of monocyte chemoattractant protein (MCP)-1, (P)RR, phospho-extracellular signal-regulated kinase (ERK)1/2, Wnt4 and active β-catenin. Treatment with DRI ameliorated proteinuria (20.33 ± 5.88 mg/day) and markedly reduced glomerular crescent formation (20.9 ± 2.6%), the induction of macrophage infiltration, (P)RR, phospho-ERK1/2, Wnt4 and active β-catenin. Furthermore, primary cultured parietal epithelial cells stimulated by recombinant prorenin showed significant increases in cell proliferation. Notably, while the ERK1/2 inhibitor PD98059 or (P)RR-specific siRNA treatment abolished the elevation in cell proliferation, DRI treatment did not abrogate this elevation. Moreover, cultured mesangial cells showed an increase in prorenin-induced MCP-1 expression. Interestingly, (P)RR or Wnt4-specific siRNA treatment or the β-catenin antagonist XAV939 inhibited the elevation of MCP-1 expression, whereas DRI did not. These results suggest that (P)RR regulates glomerular crescent formation via the ERK1/2 signaling and Wnt/β-catenin pathways during the course of anti-GBM nephritis, and that DRI mitigates the progression of crescentic GN through the reduction of (P)RR expression but not inhibition of prorenin binding to (P)RR.

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Aliskiren Regulates Neonatal Fc Receptor and IgG Metabolism with Attenuation of Anti-GBM Glomerulonephritis in Mice

Cited by 3 publications

References 50 publications

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

“Ways in which the neonatal Fc-receptor is involved in autoimmunity”

(Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis

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