The zinc fingers and homeoboxes 2 protein ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases

Macé, Camille; Avila, Maria Del Nogal; Marshall, Caroline B.; Kharlyngdoh, Joubert Banjop; Das, Ranjan; Molina‐Jijón, Eduardo; Blazquez, Hector Donoro; Shastry, Suresh; Soria, Elisabeth; Wetzels, Jack F.M.; Dijkman, Henry; Ávila-Casado, Carmen; Clement, Lionel C.; Chugh, Sumant S.

doi:10.1016/j.kint.2019.11.011

Cited by 10 publications

(31 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We collected 18-hour urine 25 and blood samples, assessed urine albumin by enzyme-linked immunosorbent assay (Bethyl Light microscopy staining of both rodent models was performed, analyzed, and interpreted by Dr. Carmen Avila-Casado. 26…”

Section: Q11mentioning

confidence: 99%

Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome

Molina‐Jijón

Gambut

Macé

et al. 2020

Kidney International

Self Cite

View full text Add to dashboard Cite

Section: Q11mentioning

confidence: 99%

Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome

Molina‐Jijón

Gambut

Macé

et al. 2020

Kidney International

Self Cite

View full text Add to dashboard Cite

“…Data on human MCD are still scarce. The same group found an increase in ZHX1 expression in podocyte nuclei from patients with active MCD, whereas ZHX2 expression was downregulated compared to controls ( 124 ).…”

Section: Podocyte Dysfunctionmentioning

confidence: 88%

“…Nuclear ZHX3 alone or in combination with ZHX2 was associated to FSGS, whereas nuclear ZHX1 was associated to MCD-like injury and podocyte Anpgtl4 upregulation in culture systems. Thus, this study provided a mechanism by which podocyte Angptl4 expression may be regulated in MCD and it proposed a plausible pathway that may be involved in the development of several forms of proteinuric kidney disease ( 124 ). Data on human MCD are still scarce.…”

Section: Podocyte Dysfunctionmentioning

confidence: 98%

“…ZHX proteins localize at the membrane as hetero- or homodimers. Using different injury models of proteinuria, Macé et al showed that translocation of ZHX proteins from the membrane into the nucleus may result in distinct types of nephrotic syndrome ( 124 ). Nuclear ZHX3 alone or in combination with ZHX2 was associated to FSGS, whereas nuclear ZHX1 was associated to MCD-like injury and podocyte Anpgtl4 upregulation in culture systems.…”

Section: Podocyte Dysfunctionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Mechanisms of Proteinuria in Minimal Change Disease

Purohit

Piani²,

Ordoñez³

et al. 2021

Front. Med.

View full text Add to dashboard Cite

Minimal change disease (MCD) is the most common type of idiopathic nephrotic syndrome in childhood and represents about 15% cases in adults. It is characterized by massive proteinuria, edema, hypoalbuminemia, and podocyte foot process effacement on electron microscopy. Clinical and experimental studies have shown an association between MCD and immune dysregulation. Given the lack of inflammatory changes or immunocomplex deposits in the kidney tissue, MCD has been traditionally thought to be mediated by an unknown circulating factor(s), probably released by T cells that directly target podocytes leading to podocyte ultrastructural changes and proteinuria. Not surprisingly, research efforts have focused on the role of T cells and podocytes in the disease process. Nevertheless, the pathogenesis of the disease remains a mystery. More recently, B cells have been postulated as an important player in the disease either by activating T cells or by releasing circulating autoantibodies against podocyte targets. There are also few reports of endothelial injury in MCD, but whether glomerular endothelial cells play a role in the disease remains unexplored. Genome-wide association studies are providing insights into the genetic susceptibility to develop the disease and found a link between MCD and certain human haplotype antigen variants. Altogether, these findings emphasize the complex interplay between the immune system, glomerular cells, and the genome, raising the possibility of distinct underlying triggers and/or mechanisms of proteinuria among patients with MCD. The heterogeneity of the disease and the lack of good animal models of MCD remain major obstacles in the understanding of MCD. In this study, we will review the most relevant candidate mediators and mechanisms of proteinuria involved in MCD and the current models of MCD-like injury.

show abstract

“…It is also involved in a wide variety of cellular functions as a structural constituent of numerous proteins, including enzymes involved in cellular signaling pathways and DNA replication, as well as transcription factors [1,2]. In addition, the zinc finger and homeobox (ZHX) family of transcription factors is highly expressed in podocytes, and these factors are also involved in glomerular disease [3]. Therefore, imbalances in zinc homoeostasis can lead to impairments in immune function, growth, cognitive function, and metabolism [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia

et al. 2021

View full text Add to dashboard Cite

Serum zinc (Zn) levels tend to be low in chronic kidney disease (CKD) patients. This cohort study was conducted to investigate the relationship between zinc deficiency and CKD progression. Patients were classified into two groups based on Zn levels < 60 μg/dl (low-Zn group, n = 160) and ≥ 60 μg/dl (high-Zn group, n = 152). The primary outcome was defined as end-stage kidney disease (ESKD) or death and was examined over a 1-year observation period. Overall, the mean Zn level was 59.6 μg/dl and the median eGFR was 20.3 ml/min/1.73 m2. The incidence of the primary outcome was higher in the low-Zn group (p<0.001). Various Cox proportional hazards models adjusted for baseline characteristics showed higher risks of the primary outcome in the low-Zn group than in the high-Zn group. Competing risks analysis showed that low Zn levels were associated with ESKD but not with death. Moreover, in propensity score-matched analysis, the low-Zn group showed a higher risk of the primary outcome [adjusted hazard ratio 1.81 (95% confidence interval 1.02, 3.24)]. Furthermore, an interaction was observed between Zn and serum albumin levels (interaction p = 0.026). The results of this study indicate that zinc deficiency is a risk factor for CKD progression.

show abstract

The zinc fingers and homeoboxes 2 protein ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases

Cited by 10 publications

References 26 publications

Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome

Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome

Molecular Mechanisms of Proteinuria in Minimal Change Disease

Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia

Contact Info

Product

Resources

About