In rat renal fibroblasts, mycophenolic acid inhibits proliferation and production of the chemokine CCL2, stimulated by tumour necrosis factor‐α

Chang, Hsiu-Ju; Wu, Vin‐Cent; Wu, Kwan‐Dun; Huang, Hongyu; Hsieh, Bor‐Shen; Chen, Ming-Fong

doi:10.1111/j.1476-5381.2010.00837.x

Cited by 3 publications

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…corticosteroids and/or calcineurin inhibitors) for the prevention of organ rejection after solid organ transplantation as well as in the therapy of autoimmune and neoplastic diseases [ 3 , 5 - 8 ]. It is known that MPA, through a nonspecific mechanism of action, can also influence non-lymphatic cells such as fibroblasts [ 3 , 9 - 14 ]. It has been proposed that MPA also has a positive effect on the progression of human kidney fibrosis [ 15 - 17 ] based on numerous in vivo [ 9 , 17 - 22 ] and in vitro studies [ 10 , 12 , 17 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of mycophenolate mofetil on kidney function and phosphorylation status of renal proteins in Alport COL4A3-deficient mice

Petrova

Schultze²,

Brandhorst³

et al. 2014

Proteome Sci

View full text Add to dashboard Cite

BackgroundWe investigated the effects of mycophenolate mofetil (MMF) on kidney function and on protein phosphorylation in a mouse model for the human Alport syndrome.MethodsCOL4A3-deficient (COL4A3−/−) mice were randomly allocated to receive a placebo (PLC COL4A3−/−) or MMF treatment (MMF COL4A3−/−). Wild type mice (WT) were used as controls. Changes in serum creatinine, total protein and blood urea nitrogen (BUN), concentrations of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG), serum protein electrophoresis, urine dipstick chemistry and sediment were measured. Changes in the phosphorylation status of renal proteins and histology were analyzed.ResultsMMF influenced kidney function and protein phosphorylation. Serum creatinine and BUN were lower in MMF treated compared to PLC treated COL4A3−/− mice. Serum albumin and alpha-1 globulins were significantly decreased while serum creatinine, alpha-2 globulins, urine dipstick protein, leukocyte esterase, hemoglobin and red blood cells were all increased in both COL4A3−/− groups compared to WT. Differential 2DE-gel analysis identified six phosphorylated kidney protein spots that were significantly altered by MMF.ConclusionsThese data suggest that the MMF treatment in this murine model moderately improved kidney function and reversed the phosphorylation status of six renal phosphoprotein spots to that seen in WT mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-014-0056-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of mycophenolate mofetil on kidney function and phosphorylation status of renal proteins in Alport COL4A3-deficient mice

Petrova

Schultze²,

Brandhorst³

et al. 2014

Proteome Sci

View full text Add to dashboard Cite

show abstract

“…MPA is a specific inhibitor of lymphocyte proliferation that noncompetitively inhibits inosine monophosphate dehydrogenase, a rate-limiting enzyme that plays a critical role in the de novo synthesis of guanosine nucleotides [44]. There is also accumulating evidence to demonstrate that MPA can have a direct effect on non-lymphoid cells and has been shown to inhibit cell proliferation and inflammatory processes in endothelial cells, smooth muscles cells, tubular epithelial cells, fibroblasts, and mesangial cells [9, 48–52]. MPA can suppress matrix protein synthesis in mesangial cells stimulated with exogenous TGF- β 1 or anti-dsDNA antibodies [9, 53].…”

Section: Interleukin-6 (Il-6)mentioning

confidence: 99%

Mediators of Inflammation and Their Effect on Resident Renal Cells: Implications in Lupus Nephritis

Yung

Cheung

Zhang

et al. 2013

Clinical and Developmental Immunology

View full text Add to dashboard Cite

Lupus nephritis affects up to 70% of patients with systemic lupus erythematosus and is a major cause of morbidity and mortality. It is characterized by a breakdown of immune tolerance, production of autoantibodies, and deposition of immune complexes within the kidney parenchyma, resulting in local inflammation and subsequent organ damage. To date, numerous mediators of inflammation have been implicated in the development and progression of lupus nephritis, and these include cytokines, chemokines, and glycosaminoglycans. Of these, type I interferons (IFNs) can increase both gene and protein expression of cytokines and chemokines associated with lupus susceptibility, and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hyaluronan have been shown to elicit both pro- and anti-inflammatory effects on infiltrating and resident renal cells depending on the status of their microenvironment. Expression of IL-6, TNF-α, type I IFNs, and hyaluronan are increased in the kidneys of patients and mice with active lupus nephritis and have been shown to contribute to disease pathogenesis. There is also evidence that despite clinical remission, ongoing inflammatory processes may occur within the glomerular and tubulointerstitial compartments of the kidney, which further promote kidney injury. In this review, we provide an overview of the synthesis and putative roles of IL-6, TNF-α, IFN-α, and hyaluronan in the pathogenesis of lupus nephritis focusing on their effects on human mesangial cells and proximal renal tubular epithelial cells.

show abstract

Molecular and Immunological Basis of Tubulo-Interstitial Injury in Lupus Nephritis: a Comprehensive Review

Yung

Chan

2016

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Lupus nephritis is an important cause of kidney failure in patients of Asian, African, or Hispanic descent. Its etiology and pathogenesis are multifactorial and remain to be elucidated. Accumulating evidence suggests that anti-double-stranded DNA (dsDNA) antibodies play a critical role in the pathogenesis, through its direct binding to cross-reactive antigens on resident renal cells or indirect binding through chromatin material to extracellular matrix components, resulting in complement activation, cell activation and proliferation, and induction of inflammatory and fibrotic processes. While tubulo-interstitial damage portends poor long-term renal prognosis, the mechanisms leading to tubulo-interstitial injury in lupus nephritis has received relatively less attention to date. Immune deposition along the tubular basement membrane is often observed in lupus nephritis and correlates with tubulo-interstitial infiltration of immune cells and interstitial fibrosis. Anti-dsDNA antibodies bind to resident renal cells, including proximal renal tubular epithelial cells, and contribute to renal inflammation and fibrosis. There is emerging evidence that epigenetic influence such as DNA methylation, histone modification, and microRNAs (miRs) also contribute to kidney fibrosis. Overexpression of miR-150 is observed in renal biopsies from patients with lupus nephritis and correlates with kidney fibrosis and chronicity score. Mycophenolate mofetil (MMF) is an established and effective standard-of-care therapy for patients with lupus nephritis. Accumulating data suggest that in addition to its immunosuppressive actions on lymphocyte proliferation, mycophenolic acid (MPA), the active metabolite of MMF, can exert a direct effect on nonimmune cells. Mediators of inflammation and fibrosis induced by anti-dsDNA antibodies in cultured proximal renal tubular epithelial cells are ameliorated by the addition of MPA, suggesting that in addition to its immunosuppressive actions, MPA may also have a beneficial effect in improving tubulo-interstitial inflammation and fibrosis through its direct action on proximal renal tubular epithelial cells.

show abstract

In rat renal fibroblasts, mycophenolic acid inhibits proliferation and production of the chemokine CCL2, stimulated by tumour necrosis factor‐α

Cited by 3 publications

References 27 publications

Effects of mycophenolate mofetil on kidney function and phosphorylation status of renal proteins in Alport COL4A3-deficient mice

Effects of mycophenolate mofetil on kidney function and phosphorylation status of renal proteins in Alport COL4A3-deficient mice

Mediators of Inflammation and Their Effect on Resident Renal Cells: Implications in Lupus Nephritis

Molecular and Immunological Basis of Tubulo-Interstitial Injury in Lupus Nephritis: a Comprehensive Review

Contact Info

Product

Resources

About