ArticleThe Journal of biological chemistry2018
Identification of direct negative cross-talk between the SLIT2 and bone morphogenetic protein-Gremlin signaling pathways.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review.Cell communication and signaling : CCS · 2024Review
- GREM1 signaling in cancer: tumor promotor and suppressor?Journal of cell communication and signaling · 2023Article
- Single Cell RNA Sequencing Reveals Human Tooth Type Identity and GuidesFrontiers in dental medicine · 2023Article
- Decoding the Mechanism behind the Pathogenesis of the Focal Segmental Glomerulosclerosis.Computational and mathematical methods in medicine · 2022Article
- SMAD4 Feedback Activates the Canonical TGF-β Family Signaling Pathways.International journal of molecular sciences · 2021Article
- Control of ovarian follicle development by TGFβ family signaling.Current opinion in endocrine and metabolic research · 2021Article
- COCO/DAND5 inhibits developmental and pathological ocular angiogenesis.EMBO molecular medicine · 2021Article
- Whole-genome methylation analysis reveals novel epigenetic perturbations of congenital scoliosis.Molecular therapy. Nucleic acids · 2021Article
- Article
- Article
- Roles of Slit Ligands and Their Roundabout (Robo) Family of Receptors in Bone Remodeling.Advances in experimental medicine and biology · 2021Review
- Osteoclasts are not a source of SLIT3.Bone research · 2020Article
- High-Throughput Sequencing to Detect Novel Likely Gene-Disrupting Variants in Pathogenesis of Sporadic Brain Arteriovenous Malformations.Frontiers in genetics · 2020Article
- No evidence of Gremlin1-mediated activation of VEGFR2 signaling in endothelial cells.The Journal of biological chemistry · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Slit guidance ligand 2 (SLIT2) is a large, secreted protein that binds roundabout (ROBO) receptors on multiple cell types, including neurons and kidney podocytes. SLIT2-ROBO-mediated signaling regulates neuronal migration and ureteric bud (UB) outgrowth during kidney development as well as glomerular filtration in adult kidneys. Additionally, SLIT2 binds Gremlin, an antagonist of bone morphogenetic proteins (BMPs), and BMP-Gremlin signaling also regulates UB formation. However, direct cross-talk between the ROBO2-SLIT2 and BMP-Gremlin signaling pathways has not been established. Here, we report the discovery of negative feedback between the SLIT2 and BMP-Gremlin signaling pathways. We found that the SLIT2-Gremlin interaction inhibited both SLIT2-ROBO2 signaling in neurons and Gremlin antagonism of BMP activity in myoblasts and fibroblasts. Furthermore, BMP2 down-regulated SLIT2 expression and promoter activity through canonical BMP signaling. Gremlin treatment, BMP receptor inhibition, and SMAD family member 4 (SMAD4) knockdown rescued BMP-mediated repression of SLIT2. BMP2 treatment of nephron progenitor cells derived from human embryonic stem cells decreased SLIT2 expression, further suggesting an interaction between the BMP2-Gremlin and SLIT2 pathways in human kidney cells. In conclusion, our study has revealed direct negative cross-talk between two pathways, previously thought to be unassociated, that may regulate both kidney development and adult tissue maintenance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.