The low affinity p75 neurotrophin receptor is down-regulated in congenital anomalies of the kidney and the urinary tract: Possible involvement in early nephrogenesis

Fédou, C.; Lescat, Ophélie; Feuillet, Guylène; Buléon, Marie; Neau, Eric; Breuil, Benjamin; Alvès, Mélinda; Batut, Julie; Blader, Patrick; Decramer, Stéphane; Saulnier-Blache, Jean Sébastien; Klein, Julie; Buffin-Meyer, Bénédicte; Schanstra, Joost P.

doi:10.1016/j.bbrc.2020.09.084

Cited by 3 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We identified eight significant GA-independent proteins (CSPG4, LMAN2, ENDOD1, ANGPTL2, PRSS8, NGFR, ROBO4, PLS3) which because they overlapped with the AF group comparisons (non-severe CAKUT versus control, severe CAKUT versus control, and severe CAKUT versus non-severe CAKUT), were hypothesized to be involved in both the presence and the severity of CAKUT. NGFR was previously reported to participate in early nephrogenesis and was shown to be altered in abundance in AF from CAKUT fetuses [24,35,36]. Moreover, the interaction network analysis between these eight proteins revealed interconnections with six proteins previously reported to be associated with CAKUT or renal maldevelopment (CDC5L, SLIT2, FRS2, GRIP1, GRIP2, and VSNL1) [37][38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 77%

“…MSigDB is a joint project of UC San Diego and the Broad Institute. Protein–protein interaction enrichment analysis was performed by using the STRING software package (https://string-db.org) [23] and protein–protein interaction network analysis was conducted using the following settings: ‘Interaction source’ = Experiments; ‘Max number of interactors to show’ = ‘1st shell’: ‘no more than 50’; ‘2nd shell’: ‘no more than 50’.…”

Section: Methodsmentioning

confidence: 99%

“…Experiments on zebrafish (Danio rerio) were approved by the French Veterinary Service and National Ethical Committee (ID: A-31-555-01 and APAPHIS #3653-2016011512005922v6) and were conducted as described previously [24] with minor modifications (see Supplementary material and methods). The efficiency of MO-pls3 to invalidate Pls3 in the zebrafish embryo has previously been demonstrated [25] [https:// zfin.org/search?category=&q=PLS3 (MO2-pls3)].…”

Section: Zebrafish Experimentsmentioning

confidence: 99%

See 2 more Smart Citations

Mapping of the amniotic fluid proteome of fetuses with congenital anomalies of the kidney and urinary tract identifies plastin 3 as a protein involved in glomerular integrity

Fédou

Camus

Lescat

et al. 2021

The Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Congenital anomalies of the kidney and the urinary tract (CAKUT) are the first cause of chronic kidney disease in childhood. Several genetic and environmental origins are associated with CAKUT, but most pathogenic pathways remain elusive. Considering the amniotic fluid (AF) composition as a proxy for fetal kidney development, we analyzed the AF proteome from non-severe CAKUT (n = 19), severe CAKUT (n = 14), and healthy control (n = 22) fetuses using LC-MS/MS. We identified 471 significant proteins that discriminated the three AF groups with 81% precision. Among them, eight proteins independent of gestational age (CSPG4, LMAN2, ENDOD1, ANGPTL2, PRSS8, NGFR, ROBO4, PLS3) were associated with both the presence and the severity of CAKUT. Among those, five were part of a protein-protein interaction network involving proteins previously identified as being potentially associated with CAKUT. The actin-bundling protein PLS3 (plastin 3) was the only protein displaying a gradually increased AF abundance from control, via non-severe, to severe CAKUT. Immunohistochemistry experiments showed that PLS3 was expressed in the human fetal as well as in both the fetal and the postnatal mouse kidney. In zebrafish embryos, depletion of PLS3 led to a general disruption of embryonic growth including reduced pronephros development. In postnatal Pls3-knockout mice, kidneys were macroscopically normal, but the glomerular ultrastructure showed thickening of the basement membrane and fusion of podocyte foot processes. These structural changes were associated with albuminuria and decreased expression of podocyte markers including Wilms' tumor-1 protein, nephrin, and podocalyxin. In conclusion, we provide the first map of the CAKUT AF proteome that will serve as a reference for future studies. Among the proteins strongly associated with CAKUT, PLS3 did surprisingly not specifically affect nephrogenesis but was found as a new contributor in the maintenance of normal kidney function, at least in part through the control of glomerular integrity.

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Zebrafish Experimentsmentioning

confidence: 99%

See 1 more Smart Citation

Mapping of the amniotic fluid proteome of fetuses with congenital anomalies of the kidney and urinary tract identifies plastin 3 as a protein involved in glomerular integrity

Fédou

Camus

Lescat

et al. 2021

The Journal of Pathology

Self Cite

View full text Add to dashboard Cite

show abstract

“…RHOA was the third gene selected from the network. Although it was regulated only by hsa-miR-185-5p, RHOA was involved in multiple described pathways including neurotrophin signaling pathway where it plays a crucial role in signal transmission important in early nephrogenesis [ 22 ]. Additionally, by investigating if the network harbors previously associated, highly penetrant CAKUT genes, we have identified only PKD1 , being a target of both miRNAs.…”

Section: Methodsmentioning

confidence: 99%

A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT

Mitrovic,

Zivotic,

Kolic

et al. 2024

BMC Genomics

View full text Add to dashboard Cite

Background The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro. Methods Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets). Results Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts. Conclusions Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.

show abstract

“…Neurotrophins and receptors are involved in different events to ensure the correct functioning of the kidney, such as growth, differentiation, and regulation of renal tubule transport. Indeed, recent functional in vivo studies, in mice models and in vitro in human patients, have revealed a close association between neurotrophin/receptor pathways and kidney diseases [27][28][29]. However, further studies using emerging animal models [30], such as zebrafish (Danio rerio), could be useful to elucidate the specific mechanisms of these pathologies.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Expression of Neurotrophins and Their Receptors in Adult Zebrafish Kidney

Cacialli

Lucini

2022

Veterinary Sciences

View full text Add to dashboard Cite

Neurotrophins and their receptors are involved in the development and maintenance of neuronal populations. Different reports have shown that all neurotrophin/receptor pathways can also play a role in several non-neuronal tissues in vertebrates, including the kidney. These signaling pathways are involved in different events to ensure the correct functioning of the kidney, such as growth, differentiation, and regulation of renal tubule transport. Previous studies in some fish species have identified the neurotrophins and receptors in the kidney. In this study, for the first time, we compare the expression profiles (mRNA and protein) of all neurotrophin/receptor pathways in the kidney of the adult zebrafish. We quantify the levels of mRNA by using qPCR and identify the expression pattern of each neurotrophin/receptor pathway by in situ hybridization. Next, we detect the proteins using Western blotting and immunohistochemistry. Our results show that among all neurotrophins analyzed, NT-3/TrkC is the most expressed in the glomerule and tubule and in the hematopoietic cells, similar to what has been reported in the mammalian kidney.

show abstract

The low affinity p75 neurotrophin receptor is down-regulated in congenital anomalies of the kidney and the urinary tract: Possible involvement in early nephrogenesis

Cited by 3 publications

References 19 publications

Mapping of the amniotic fluid proteome of fetuses with congenital anomalies of the kidney and urinary tract identifies plastin 3 as a protein involved in glomerular integrity

Mapping of the amniotic fluid proteome of fetuses with congenital anomalies of the kidney and urinary tract identifies plastin 3 as a protein involved in glomerular integrity

A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT

Analysis of the Expression of Neurotrophins and Their Receptors in Adult Zebrafish Kidney

Contact Info

Product

Resources

About