Abstract:
:Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lung fibrosis, little is known regarding its role in renal fibrosis. Here we determine whether LOXL2 influences kidney disease in COL4A3 (-/-) Alport mice. These mice were treated with a small molecule inhibitor selective for LOXL2 or with vehicle and assessed for glomerular sclerosis and fibrosis, albuminuria, blood urea nitrogen, lifespan, pro-fibrotic gene expression and ultrastructure of the glomerular basement membrane. Laminin α2 deposition in the glomerular basement membrane and mesangial filopodial invasion of the glomerular capillaries were also assessed. LOXL2 inhibition significantly reduced interstitial fibrosis and mRNA expression of MMP-2, MMP-9, TGF-β1, and TNF-α. LOXL2 inhibitor treatment also reduced glomerulosclerosis, expression of MMP-10, MMP-12, and MCP-1 mRNA in glomeruli, and decreased albuminuria and blood urea nitrogen. Mesangial filopodial invasion of the capillary tufts was blunted, as was laminin α2 deposition in the glomerular basement membrane, and glomerular basement membrane ultrastructure was normalized. There was no effect on lifespan. Thus, LOXL2 plays an important role in promoting both glomerular and interstitial pathogenesis associated with Alport syndrome in mice. Other etiologies of chronic kidney disease are implicated with our observations.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Cosgrove D,Dufek B,Meehan DT,Delimont D,Hartnett M,Samuelson G,Gratton MA,Phillips G,MacKenna DA,Bain Gdoi
10.1016/j.kint.2018.02.024subject
Has Abstractpub_date
2018-08-01 00:00:00pages
303-314issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(18)30215-1journal_volume
94pub_type
杂志文章abstract:BACKGROUND:Autosomal-dominant medullary cystic kidney disease (ADMCKD), a hereditary chronic interstitial nephropathy, recently attracted attention because of the cloning or mapping of certain gene loci, namely NPHP1, NPHP2 and NPHP3 for familial juvenile nephronophthisis (NPH) and MCKD1 and MCKD2 for the adult form of...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid581.x
更新日期:2002-10-01 00:00:00
abstract::In the course of studying the genetics of chlorambucil mutagenesis, we have uncovered a new model for autosomal polycystic kidney disease (PKD). In the homozygous condition, the gene, jcpk, causes a very severe disease characterized by cysts in all segments of the nephron. Death usually occurs before 10 days of age. E...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.69
更新日期:1995-02-01 00:00:00
abstract::Despite the increasing knowledge of the role of gangliosides in normal and diseased tissues, little is known of the presence, distribution and functions of these molecules in the kidney. In this study we analyzed the main gangliosides of isolated glomeruli and cortical, medullary and papillary fractions of the human, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.14
更新日期:1994-01-01 00:00:00
abstract::Sodium thiosulfate, a reversible oxidation product of hydrogen sulfide, has vasodilating and anti-oxidative properties, making it an attractive agent to alleviate damaging effects of hypertension. In experimental settings, inhibition of nitric oxide synthase causes hypertension, renal dysfunction and damage. We hypoth...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.02.020
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:There is accumulating evidence that adult bone marrow (BM) cells show unexpected plasticity, and can differentiate into a wide range of specialized cells. In the case of intrinsic renal glomerular cells, BM-derived cells have been reported to differentiate into both mesangial cells and podocytes. However, th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00291.x
更新日期:2005-05-01 00:00:00
abstract::The role of calcitonin on the calcemic response to parathyroid hormone (PTH) in renal failure has not been evaluated previously. Often animal studies evaluating the calcemic response to PTH in renal failure are performed in thyroparathyroidectomized (TPTX) animals, and thus eliminate any potential physiologic effect o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.203
更新日期:1991-08-01 00:00:00
abstract:BACKGROUND:Although several kinds of evidence suggest that glycosaminoglycans (GAGs) and proteoglycans (PGs) may contribute to the development of beta2-microglobulin-related (Abeta2m) amyloidosis, the precise roles of these molecules for the development of Abeta2m amyloidosis are poorly understood. METHODS:We investig...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00167.x
更新日期:2003-09-01 00:00:00
abstract::Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients ...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.03.014
更新日期:2017-09-01 00:00:00
abstract::Pathologic calcification is a significant cause of increased morbidity and mortality in patients with chronic kidney disease. The precise mechanisms of ectopic calcification are not fully elucidated, but it is known to be caused by an imbalance of procalcific and anticalcific factors. In the chronic kidney disease pop...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2015.12.046
更新日期:2016-05-01 00:00:00
abstract::ESKD patients have a large burden of disease, with high rates of readmission to hospital compared with the general population. A readmission after an acute index hospital discharge is either planned or unplanned. A proportion of unplanned readmissions are potentially avoidable, and could have been prevented with optim...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2015.307
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:C-peptide has been reported to have biological effects on renal function early in the course of diabetes. This investigation was initiated to elucidate and amplify these findings with respect to protein leakage, hyperfiltration and renal functional reserve in diabetic rats. METHODS:Acute effects of 140 minu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00074.x
更新日期:1998-09-01 00:00:00
abstract::Most epidemiologic data, thus far, have focused on short-term outcomes of acute kidney injury (AKI). Lo et al. correlate AKI with long-term outcomes. The concept of 'uremic memory' sheds light on the importance of AKI and its permanent imprint. The focus of research should be on prevention of an episode of AKI, when p...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.314
更新日期:2009-10-01 00:00:00
abstract::The in vitro heparin sensitivity of 18 nephrotic children was compared with that of 10 normal children and 13 children with other renal diseases. The influence of age on the heparin sensitivity of 52 normal subjects (aged 12 to 85 years) was also studied. The heparin sensitivity was calculated from the dose-response c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.155
更新日期:1987-06-01 00:00:00
abstract::Tissandié and colleagues report in this issue on their studies of IgA1 glycosylation and biological activities of IgA1-containing circulating immune complexes in patients with alcoholic cirrhosis who developed secondary renal disease with IgA deposits, secondary IgA nephropathy. Their seminal findings demonstrate abno...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2011.302
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Since the cloning of the gene for autosomal dominant polycystic kidney disease type 2 (PKD2), approximately 40 different mutations of that gene have been reported to be associated with the disease. The relationship between the PKD2 genotype and phenotype, however, remains unclear. METHODS:Detailed clinical ...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1046/j.1523-1755.2000.00989.x
更新日期:2000-04-01 00:00:00
abstract::Insulin-like growth factor I (IGF-I) has been found in the kidney, particularly in the collecting duct in the rat. Since cultured rabbit collecting duct cells constitute a convenient system for in vitro studies, we have examined whether these cells secrete IGF-I. Culture medium conditioned by collecting duct cells was...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.3
更新日期:1991-01-01 00:00:00
abstract::Colony stimulating factor-1 (CSF-1) is a chemoattractant and growth factor for macrophages. In autoimmune MRL-lpr mice, CSF-1 is detected in the circulation and there is an increase in CSF-1 transcripts and macrophages in the kidney. The purpose of this study was to establish whether the MRL-lpr kidney is responsible ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.9
更新日期:1996-01-01 00:00:00
abstract::This study examined the utility of interleukin-10 (IL-10), a cytokine with potent anti-macrophage and anti-Th1 activity, in the treatment of experimental anti-glomerular basement membrane (GBM) nephritis in the rat. Accelerated anti-GBM disease was induced in Sprague-Dawley rats by immunization with rabbit IgG, follow...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.248
更新日期:1997-06-01 00:00:00
abstract::The relative importance of sarcopenia and its individual components as independent predictors of mortality in the dialysis population has not been determined. We estimated whole-body muscle mass using pre-dialysis bioimpedance spectroscopy measurements in 645 ACTIVE/ADIPOSE-enrolled prevalent hemodialysis patients fro...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.01.024
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:Vascular access failure is the main cause of morbidity in hemodialysis. Venous stenosis and subsequent thrombosis, as the result of intimal hyperplasia, is the major cause of vascular access failure. Intimal hyperplasia of the arteriovenous fistula (AVF) closely resembles the main histopathologic feature of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00120.x
更新日期:2003-08-01 00:00:00
abstract::In summary, it is evident that malnutrition is highly prevalent in ESRD patients. This is clearly related to multiple factors encountered during the pre-dialysis stage, as well as during maintenance dialysis therapy. A body of evidence highlights the existence of relationship between malnutrition and outcome in this p...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.323
更新日期:1996-08-01 00:00:00
abstract::Gain-of-function variants in CFB encoding factor B (FB), a component of the alternative pathway C3 convertase, have been reported in a minority of patients with aHUS and result in massive C3 activation. Zhang et al. describe the functional characterization of a novel FB variant (p.Ser367Arg) that they identified in 2 ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2020.06.026
更新日期:2020-11-01 00:00:00
abstract::The beneficial effects of post-insult administration of pentoxifylline, a novel hemorheologic agent experimentally studied in various ischemic diseases, were evaluated in two models of acute renal failure (ARF): direct nephrotoxicity (mercuric chloride 4 mg/kg via femoral vein) and hemoglobinuria (glycerol 10 ml/kg i....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.218
更新日期:1989-09-01 00:00:00
abstract:BACKGROUND:Although the existence of multiple isoforms of plasma membrane calcium ATPase (PMCA) is now well documented, their biological functions are not yet known. In this study, we set out to investigate the potential role of PMCA isoforms, previously identified in renal cortical tissue, in tubular reabsorption of c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00736.x
更新日期:1999-11-01 00:00:00
abstract::Recent studies suggest the presence of local angiotensin generating system in the kidney. By using in situ hybridization technique, mRNA for angiotensinogen has been shown to be present in the proximal tubule. In the present study, we have attempted to examine the production of angiotensinogen and renin-like activity ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.117
更新日期:1991-05-01 00:00:00
abstract::The hypercalcemia of malignancy is mediated by complex and heterogeneous mechanisms. Once thought of as a simple paraneoplastic syndrome mediated by the effects of tumor production of PTH, it is now clear that multiple mechanisms are involved and that these mechanisms involve abnormalities in calcium transport in bone...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.21
更新日期:1987-01-01 00:00:00
abstract:BACKGROUND:Aquaporin-2 (AQP-2) proteins are mainly expressed at the apical region of the collecting duct cells. We previously reported three different mutations in the C-terminus of AQP-2 that all-cause autosomal-dominant nephrogenic diabetes insipidus. When one of these mutant AQP-2s was expressed in Madin-Darby canin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00654.x
更新日期:2005-11-01 00:00:00
abstract::A new study in dialysis patients demonstrates that more than one-third of rehospitalizations within 30 days of discharge occur within the first week, and these rehospitalizations are associated with worse survival. Imposing a penalty on the dialysis provider for these rehospitalizations, as mandated by the Hospital Re...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.04.046
更新日期:2017-10-01 00:00:00
abstract::Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features in the setting of advanced chronic renal failure (CRF). Although the underlying mechanisms are ill-understood, clinical and experimental evidence points to both PTH receptor down-regulation and post-receptor abnormalit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.79
更新日期:1994-02-01 00:00:00
abstract::Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-k...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.134
更新日期:2009-07-01 00:00:00