Myelomeningocele genotype–phenotype correlation findings in cilia, HH, PCP, and WNT signaling pathways

Ortiz‐Cruz, Gabriela; Aguayo-Gómez, Adolfo; Luna‐Muñoz, Leonora; Muñoz‐Téllez, Luis A.; Mutchinick, Osvaldo M.

doi:10.1002/bdr2.1872

Cited by 7 publications

(7 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disruptions in COPII-mediated vesicular ER-to-Golgi transport have been linked to SB via the role of COPII in transporting key components of the planar cell polarity (non-canonical Wnt) pathway 57-59 . Wnt signalling, as well as Hedgehog signalling, have been associated with NTDs through their regulatory role in neural tube closure 60,61 , and were both upregulated in case placentae. Notably, cases also had downregulation in genesets involved in glycosylation (a protein or lipid modification that largely occurs in the Golgi 62 ), and upregulation in protein synthesis (which occurs mainly on the ribosomes of the ER), which could both be compensatory for reductions in COPII-mediated ER-to-Golgi protein transport.…”

Section: Discussionmentioning

confidence: 99%

Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study

White

Arif-Pardy

Mieghem

et al. 2023

Preprint

View full text Add to dashboard Cite

To improve outcomes of fetuses with spina bifida (SB), better knowledge is needed on the molecular drivers of SB and its comorbidities. We have recently shown in historical data that SB often associates with reduced fetal growth. We here use placental transcriptome sequencing and a novel nutrient-focused analysis pipeline to determine whether this association is due to placental dysfunction. We show that fetuses with SB have dysregulation in placental gene networks that play a role in nutrient transport, branching angiogenesis, and immune/inflammatory processes. Several of these networks are sensitive to multiple micronutrients, other than the well-known folic acid, and this deserves further investigation. An improved understanding of placental phenotype in fetuses with SB may help identify novel mechanisms associated with SB and its comorbidities, and reveal new targets to improve fetal outcomes in this population.

show abstract

Section: Discussionmentioning

confidence: 99%

Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study

White

Arif-Pardy

Mieghem

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The initiation and resolution of require mechanisms for the comprehensive reprogramming of macrophage interactions with epithelial cells and fibroblasts [ 15 ]. These mechanisms involve several transcription factors, including nuclear factor (NF)-κB [ 16 ], interferon regulatory factors (IRFs) [ 17 ], signal transducers and activators of transcription (STATs) [ 18 ], wingless-INT (Wnt) [ 19 ], and activator protein 1 (AP-1) [ 20 ]. Twist1, a member of the basic helix–loop–helix family of transcription factors, has multiple functions that are associated with fibrotic diseases and tumor progression [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3

Sun

Wei

et al. 2022

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Renal interstitial fibrosis is the pathological basis of end-stage renal disease, in which the heterogeneity of macrophages in renal microenvironment plays an important role. However, the molecular mechanisms of macrophage plasticity during renal fibrosis progression remain unclear. In this study, we found for the first time that increased expression of Twist1 in macrophages was significantly associated with the severity of renal fibrosis in IgA nephropathy patients and mice with unilateral ureteral obstruction (UUO). Ablation of Twist1 in macrophages markedly alleviated renal tubular injury and renal fibrosis in UUO mice, accompanied by a lower extent of macrophage infiltration and M2 polarization in the kidney. The knockdown of Twist1 inhibited the chemotaxis and migration of macrophages, at least partially, through the CCL2/CCR2 axis. Twist1 downregulation inhibited M2 macrophage polarization and reduced the secretion of the profibrotic factors Arg-1, MR (CD206), IL-10, and TGF-β. Galectin-3 was decreased in the macrophages of the conditional Twist1-deficient mice, and Twist1 was shown to directly activate galectin-3 transcription. Up-regulation of galectin-3 recovered Twist1-mediated M2 macrophage polarization. In conclusion, Twist1/galectin-3 signaling regulates macrophage plasticity (M2 phenotype) and promotes renal fibrosis. This study could suggest new strategies for delaying kidney fibrosis in patients with chronic kidney disease.

show abstract

“…16a ) in their work. The PLCB4 protein (Phospholipase C Beta 4) belongs to a group of enzymes that hydrolyze phospholipids [ 30 ]. PLCB4 expression was significantly higher in highly activated Wnt cell lines.…”

Section: Resultsmentioning

confidence: 99%

Embryonic organizer formation disorder leads to multiorgan dysplasia in Down syndrome

et al. 2022

View full text Add to dashboard Cite

Despite the high prevalence of Down syndrome (DS) and early identification of the cause (trisomy 21), its molecular pathogenesis has been poorly understood and specific treatments have consequently been practically unavailable. A number of medical conditions throughout the body associated with DS have prompted us to investigate its molecular etiology from the viewpoint of the embryonic organizer, which can steer the development of surrounding cells into specific organs and tissues. We established a DS zebrafish model by overexpressing the human DYRK1A gene, a highly haploinsufficient gene located at the “critical region” within 21q22. We found that both embryonic organizer and body axis were significantly impaired during early embryogenesis, producing abnormalities of the nervous, heart, visceral, and blood systems, similar to those observed with DS. Quantitative phosphoproteome analysis and related assays demonstrated that the DYRK1A-overexpressed zebrafish embryos had anomalous phosphorylation of β-catenin and Hsp90ab1, resulting in Wnt signaling enhancement and TGF-β inhibition. We found an uncovered ectopic molecular mechanism present in amniocytes from fetuses diagnosed with DS and isolated hematopoietic stem cells (HSCs) of DS patients. Importantly, the abnormal proliferation of DS HSCs could be recovered by switching the balance between Wnt and TGF-β signaling in vitro. Our findings provide a novel molecular pathogenic mechanism in which ectopic Wnt and TGF-β lead to DS physical dysplasia, suggesting potential targeted therapies for DS.

show abstract

Myelomeningocele genotype–phenotype correlation findings in cilia, HH, PCP, and WNT signaling pathways

Cited by 7 publications

References 54 publications

Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study

Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study

Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3

Embryonic organizer formation disorder leads to multiorgan dysplasia in Down syndrome

Contact Info

Product

Resources

About