Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice.

Zoja, Carla; Liu, Xue Hui; Donadelli, Roberta; Abbate, Mauro; Testa, Davide; Corna, Daniela; Taraboletti, Giulia; Vecchi, Annunciata; Dong, Qiang; Rollins, Barrett J.; Bertani, Tullio; Remuzzi, Giuseppe

doi:10.1681/asn.v85720

Cited by 77 publications

(10 citation statements)

References 32 publications

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“…MCP-1 is a monocyte chemotactic factor that binds CCR2 on monocytes and promotes monocyte mobilization from bone marrow, recruitment to local tissues, and differentiation into macrophages ( 73 , 90 ). MCP-1 has been implicated in inflammation and kidney diseases ( 73 , 75 , 79 , 91 ). CXCL10 is also increased after injury in Ret UB del kidneys.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, Timp-1, MCP-1, CXCL10, and IL-1ra were significantly higher in gent-exposed Ret UB del kidneys compared to gentamicin-exposed littermates with normal nephron number (Figure 7). Given that Timp-1, MCP-1 and CXCL10 have all been implicated in renal inflammatory diseases (64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79), we focused on these cytokines for further analysis. We found that while both control and Ret UB del mice had significantly increased expression of Timp-1 and MCP-1 after gentamicin, the increase was much greater in Ret UB del mice.…”

Section: Ret Ub Del Mice Have a Unique Inflammatory Response To Genta...mentioning

confidence: 99%

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Low nephron endowment increases susceptibility to renal stress and chronic kidney disease

Good¹,

Li²,

Hurst³

et al. 2023

JCI Insight

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Preterm birth results in low nephron endowment and increased risk of acute kidney injury (AKI) and chronic kidney disease (CKD). To understand the pathogenesis of AKI and CKD in preterm humans, we generated novel mouse models with a 30-70% reduction in nephron number by inhibiting or deleting Ret tyrosine kinase in the developing ureteric bud. These mice developed glomerular and tubular hypertrophy followed by the transition to CKD, recapitulating the renal pathological changes seen in humans born preterm. We injected neonatal mice with gentamicin, a ubiquitous nephrotoxic exposure in preterm infants, and detected more severe proximal tubular injury in mice with low nephron number compared to controls with normal nephron number.Mice with low nephron number have reduced proliferative repair with more rapid development of CKD.Furthermore, mice had more profound inflammation with highly elevated levels of MCP-1 and CXCL10, produced in part by damaged proximal tubules. Our study directly links low nephron endowment with postnatal renal hypertrophy, which in this model is maladaptive and results in CKD. Underdeveloped kidneys are more susceptible to gentamicin-induced AKI, suggesting that AKI in the setting of low nephron number is more severe and further increases the risk of CKD in this vulnerable population.

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Section: Discussionmentioning

confidence: 99%

Section: Ret Ub Del Mice Have a Unique Inflammatory Response To Genta...mentioning

confidence: 99%

Low nephron endowment increases susceptibility to renal stress and chronic kidney disease

Good¹,

Li²,

Hurst³

et al. 2023

JCI Insight

View full text Add to dashboard Cite

show abstract

“…MCP-1 is induced by type I interferons and multiple pro-inflammatory cytokines ( 38 ). MCP-1 has potent chemiotactic activity, especially for macrophages and neutrophils ( 39 – 41 ), and thus may act to promote leucocyte recruitment to the kidney. Consistent with this possibility, it was shown to increase prior to proteinuria in LN flares ( 42 ) and higher levels are associated with worse clinical outcomes ( 20 , 42 – 45 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Urinary Biomarker Panel to Accurately Diagnose and Predict Response to Therapy in Lupus Nephritis

et al. 2022

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BackgroundWe have previously shown that 15 urinary biomarkers (of 129 tested by Luminex), discriminate between active Lupus Nephritis (ALN) and non-LN patients. The aim of this study was to evaluate the ability of these 15 previously-identified urinary biomarkers to predict treatment responses to conventional therapy, and for the most predictive of these biomarkers to validate their utility to identify ALN patients in an independent prospectively-acquired lupus cohort.MethodsOur study had a 3-stage approach. In stage 1, we used Luminex to examine whether our previously identified urinary biomarkers at the time of the renal flare ( ± 3 months) or 12 ± 3 months after treatment of biopsy-proven ALN could predict treatment responses. In stage 2, a larger prospectively-acquired cross-sectional cohort was used to further validate the utility of the most predictive urinary biomarkers (identified in stage 1) to detect ALN patients. In this 2nd stage, cut-offs with the best operating characteristics to detect ALN patients were produced for each biomarker and different combinations and/or numbers of elevated biomarkers needed to accurately identify ALN patients were analyzed. In stage 3, we aimed to further corroborate the sensitivity of the cut-offs created in stage 2 to detect ALN patients in a biopsy-proven ALN cohort who had a urine sample collection within 3 months of their biopsy.ResultsTwenty-one patients were included in stage 1. Twelve (57.1%), 4 (19.1%), and 5 (23.8%) patients had a complete (CR), partial (PR) and no (NR) remission at 24 ± 3 months, respectively. The percentage decrease following 12 ± 3 months of treatment for Adiponectin, MCP-1, sVCAM-1, PF4, IL-15 and vWF was significantly higher in patients with CR in comparison to those with PR/NR. In stage 2, a total of 247 SLE patients were included, of which 24 (9.7%) had ALN, 79 (31.9%) had LN in remission (RLN) and 144 (58.3%) were non-LN (NLN) patients. Based on the combinations of biomarkers with the best operating characteristics we propose “rule out” and “rule in” ALN criteria. In stage 3, 53 biopsy-proven ALN patients were included, 35 with proliferative LN and 18 with non-proliferative ALN, demonstrating that our “rule in ALN” criteria operate better in detecting active proliferative than non-proliferative classes.ConclusionsOur results provide further evidence to support the role of Adiponectin, MCP-1, sVCAM-1 and PF4 in the detection of proliferative ALN cases. We further show the clinical utility of measuring multiple rather than a single biomarker and we propose novel “rule in” and “rule out” criteria for the detection of proliferative ALN with excellent operating characteristics.

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“…MCP-1 is produced by tubular epithelial cells resulting in increased cytokine and adhesion molecule expression which further activates tubular epithelial cells, increasing the inflammatory response [ 65 ]. Animal models of SLE have demonstrated the role of MCP-1 as a driver of inflammatory cell infiltration and have suggested a potential therapeutic target role, as MCP-1 deletion reduced renal inflammation and proteinuria, and prolonged survival [ 67 , 68 ]. As a urinary biomarker, MCP-1 level has been demonstrated to increase in JSLE LN flares, to be a fair-good predictor of LN activity and to be higher in non-responders to therapy [ 44 , 45 , 48 , 50 , 54 ].…”

Section: Renal Biomarkersmentioning

confidence: 99%

Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus

Greenan-Barrett

Doolan

Shah

et al. 2021

IJMS

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Juvenile systemic lupus erythematosus (JSLE) is characterised by onset before 18 years of age and more severe disease phenotype, increased morbidity and mortality compared to adult-onset SLE. Management strategies in JSLE rely heavily on evidence derived from adult-onset SLE studies; therefore, identifying biomarkers associated with the disease pathogenesis and reflecting particularities of JSLE clinical phenotype holds promise for better patient management and improved outcomes. This narrative review summarises the evidence related to various traditional and novel biomarkers that have shown a promising role in identifying and predicting specific organ involvement in JSLE and appraises the evidence regarding their clinical utility, focusing in particular on renal biomarkers, while also emphasising the research into cardiovascular, haematological, neurological, skin and joint disease-related JSLE biomarkers, as well as genetic biomarkers with potential clinical applications.

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Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice.

Cited by 77 publications

References 32 publications

Low nephron endowment increases susceptibility to renal stress and chronic kidney disease

Low nephron endowment increases susceptibility to renal stress and chronic kidney disease

Identification and Validation of a Urinary Biomarker Panel to Accurately Diagnose and Predict Response to Therapy in Lupus Nephritis

Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus

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