Mesangial Cells in Lupus Nephritis

The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU) and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly increased. To better understand the role and mechanisms by which this pathway contributes to the progression of LN, we analyzed the expression and effects of NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1 expression, NEU activity, and IL-6 production are significantly increased in stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL-6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and in renal sections from nephritic MRL/lpr mice. Together, our results suggest that NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG-receptor complex signaling pathway.

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Retinoic acid-inducible gene-I (RIG-I) is induced by IFN- in human mesangial cells in culture: possible involvement of RIG-I in the inflammation in lupus nephritis

Lupus ◽

10.1177/0961203309360540 ◽

2010 ◽

Vol 19 (7) ◽

pp. 830-836 ◽

Cited By ~ 15

Author(s):

T. Imaizumi ◽

H. Tanaka ◽

A. Tajima ◽

K. Tsuruga ◽

E. Oki ◽

...

Keyword(s):

Retinoic Acid ◽

Lupus Nephritis ◽

Mesangial Cells ◽

Human Mesangial Cells ◽

Cells In Culture ◽

Inducible Gene

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The Urinary Exosomal miRNA Expression Profile is Predictive of Clinical Response in Lupus Nephritis

International Journal of Molecular Sciences ◽

10.3390/ijms21041372 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1372 ◽

Cited By ~ 4

Author(s):

Eloi Garcia-Vives ◽

Cristina Solé ◽

Teresa Moliné ◽

Marta Vidal ◽

Irene Agraz ◽

...

Keyword(s):

Lupus Nephritis ◽

Clinical Response ◽

Mesangial Cells ◽

Area Under The Curve ◽

Mirna Expression Profile ◽

Renal Tissue ◽

Renal Outcome ◽

Protein Levels ◽

Urinary Exosomes

Data on exosomal-derived urinary miRNAs have identified several miRNAs associated with disease activity and fibrosis formation, but studies on prognosis are lacking. We conducted a qPCR array screening on urinary exosomes from 14 patients with biopsy-proven proliferative lupus glomerulonephritis with a renal outcome of clinical response (n = 7) and non-response (n = 7) following therapy. Validation studies were performed by qRT-PCR in a new lupus nephritis (LN) cohort (responders = 22 and non-responders = 21). Responder patients expressed significantly increased levels of miR-31, miR-107, and miR-135b-5p in urine and renal tissue compared to non-responders. MiR-135b exhibited the best predictive value to discriminate responder patients (area under the curve = 0.783). In vitro studies showed exosome-derived miR-31, miR-107, and miR-135b-5p expression to be mainly produced by tubular renal cells stimulated with inflammatory cytokines (e.g IL1, TNFα, IFNα and IL6). Uptake of urinary exosomes from responders by mesangial cells was superior compared to that from non-responders (90% vs. 50%, p < 0.0001). HIF1A was identified as a potential common target, and low protein levels were found in non-responder renal biopsies. HIF1A inhibition reduced mesangial proliferation and IL-8, CCL2, CCL3, and CXCL1 mesangial cell production and IL-6/VCAM-1 in endothelial cells. Urinary exosomal miR-135b-5p, miR-107, and miR-31 are promising novel markers for clinical outcomes, regulating LN renal recovery by HIF1A inhibition.

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Radical Improvement of Signs and Symptoms in Systemic Lupus Erythematosus when Treated with Hemodiafiltration with Endogenous Reinfusion Dialysis

Case Reports in Nephrology and Dialysis ◽

10.1159/000381395 ◽

2015 ◽

Vol 5 (1) ◽

pp. 106-112 ◽

Cited By ~ 1

Author(s):

Francesco Giuseppe Solano ◽

Elisa Bellei ◽

Aurora Cuoghi ◽

Marialuisa Caiazzo ◽

Francesco Bruni

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Joint Pain ◽

Mesangial Cells ◽

Skin Lesions ◽

Dialysis Session ◽

Skin Damage ◽

Systemic Lupus ◽

Conjunctival Hyperemia

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). In the kidney, immune complexes and autoantibodies activate mesangial cells that secrete cytokines that can further amplify inflammatory processes. We present the case of a 42-year-old woman with lupus nephritis accompanied by periods of exacerbation of SLE, with necrotic-like skin lesions, psoriatic arthritis without skin psoriasis, purpura of the lower limb, petechial rash, joint pain, fever, eyelid edema with bilateral conjunctival hyperemia and itching. The patient underwent a dialytic treatment of hemodiafiltration with endogenous reinfusion. The technique uses the super-high-flux membrane Synclear 02 (SUPRA treatment) coupled with an adsorbent cartridge that has affinity for many toxins and mediators. Fever and joint pain were immediately reduced after treatment and, subsequently, there was a notable reduction of the skin damage. Prednisone and immunosuppressive drugs were gradually reduced until complete suspension. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer was performed for identification of proteins captured by a resin bed during a dialysis session of the patient. This technique identified several biomarkers of kidney injuries, uremic toxins, fragments of immunoglobulins, antigens involved in antiphospholipid syndrome and a new marker (α-defensin) that correlated significantly with disease activity. The removal of these different proteins could possibly provide an explanation of the improvement in the patient's symptoms and the normalization of her SLE. SUPRA coupled with an adsorption may be a promising new technique for the treatment of lupus nephritis.

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