ArticleAmerican journal of physiology. Renal physiology2011
Inhibition of the protein kinase MK-2 protects podocytes from nephrotic syndrome-related injury.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 21 citations in OpenAlex.
- Mesangial cell-derived CircRNAs in chronic glomerulonephritis: RNA sequencing and bioinformatics analysis.Renal failure · 2024Article
- Mycophenolic acid directly protects podocytes by preserving the actin cytoskeleton and increasing cell survival.Scientific reports · 2023Article
- A novel podocyte protein, R3h domain containing-like, inhibits TGF-β-induced p38 MAPK and regulates the structure of podocytes and glomerular basement membrane.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Assessing the Impact of Losmapimod on Proteinuria in Idiopathic Focal Segmental Glomerulosclerosis.Kidney international reports · 2020Article
- Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury.International journal of molecular sciences · 2020Article
- Pharmacological and genetic inhibition of downstream targets of p38 MAPK in experimental nephrotic syndrome.American journal of physiology. Renal physiology · 2018Article
- Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models.Scientific reports · 2016Article
- Drug discovery in focal and segmental glomerulosclerosis.Kidney international · 2016Review
- Targeting Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts To Lead Small Molecule Inhibitors to Clinical Trials.Journal of medicinal chemistry · 2016Review
- APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A Podocyte-Based Automated Screening Assay Identifies Protective Small Molecules.Journal of the American Society of Nephrology : JASN · 2015Article
- Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples.Journal of Zhejiang University. Science. B · 2015Article
- Albumin-induced podocyte injury and protection are associated with regulation of COX-2.Kidney international · 2014Article
- Crucial roles of the protein kinases MK2 and MK3 in a mouse model of glomerulonephritis.PloS one · 2013Article
- Childhood nephrotic syndrome--current and future therapies.Nature reviews. Nephrology · 2012Review
- Comparison of direct action of thiazolidinediones and glucocorticoids on renal podocytes: protection from injury and molecular effects.Molecular pharmacology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
While mitogen-activated protein kinase (MAPK) activation has been implicated in the pathogenesis of various glomerular diseases, including nephrotic syndrome (NS), its specific role in podocyte injury is not known. We hypothesized that MK-2, a downstream substrate of p38 MAPK, mediates the adverse effects of this pathway and that inhibition of MK-2 would protect podocytes from NS-related injury. Using cultured podocytes, we analyzed 1) the roles of MK-2 and p38 MAPK in puromycin aminonucleoside (PAN)-induced podocyte injury; 2) the ability of specific MK-2 and p38 MAPK inhibitors to protect podocytes against injury; 3) the role of serum albumin, known to induce podocyte injury, in activating p38 MAPK/MK-2 signaling; and 4) the role of p38 MAPK/MK-2 signaling in the expression of Cox-2, an enzyme associated with podocyte injury. Treatment with protein kinase inhibitors specific for both MK-2 (C23, a pyrrolopyridine-type compound) or p38 MAPK (SB203580) reduced PAN-induced podocyte injury and actin cytoskeletal disruption. Both inhibitors reduced baseline podocyte p38 MAPK/MK-2 signaling, as measured by the degree of phosphorylation of HSPB1, a downstream substrate of MK-2, but exhibited disparate effects on upstream signaling. Serum albumin activated p38 MAPK/MK-2 signaling and induced Cox-2 expression, and these responses were blocked by both inhibitors. Given the critical importance of podocyte injury to both NS and other progressive glomerular diseases, these data suggest an important role for p38 MAPK/MK-2 signaling in podocyte injury and identify MK-2 inhibition as a promising potential therapeutic strategy to protect podocytes in various glomerular diseases.
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.