ArticlePloS one2014
Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 66 citations in OpenAlex.
- Accelerated basement membrane remodeling and serum matrix fragments as biomarkers of fibrosis in Alport syndrome.Cell reports · 2026Article
- Glomerular basement membrane structural integrity dictates trans-tissue deposition of laminin in the kidney.Cell reports · 2026Article
- Endothelial cell-released CD93 contributes to podocyte injury in idiopathic nephrotic syndrome.Science translational medicine · 2026Article
- Extracellular matrices regulate extravasation journey of leukocytes and inflammatory tissue fate.eLife · 2025Review
- The role of tetraspanins in organ fibrosis: mechanisms and therapeutic perspectives.Journal of translational medicine · 2025Review
- Endothelin receptor antagonists in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Role of the Innate Immune Response in Glomerular Disease Pathogenesis: Focus on Podocytes.Cells · 2024Review
- Progress in therapeutic targets on podocyte for Alport syndrome.Journal of translational internal medicine · 2024Article
- The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease.JCI insight · 2024Article
- Ramipril therapy in integrin α1-null, autosomal recessive Alport mice triples lifespan: mechanistic clues from RNA-seq analysis.The Journal of pathology · 2024Article
- Dual inhibition of the endothelin and angiotensin receptor ameliorates renal and inner ear pathologies in Alport mice.The Journal of pathology · 2023Article
- Glomerular basement membrane deposition of collagen α1(III) in Alport glomeruli by mesangial filopodia injures podocytes via aberrant signaling through DDR1 and integrin α2β1.The Journal of pathology · 2022Article
- Tensin 2-deficient nephropathy: mechanosensitive nephropathy, genetic susceptibility.Experimental animals · 2022Review
- Article
- A novel model of nephrotic syndrome results from a point mutation in Lama5 and is modified by genetic background.Kidney international · 2022Article
- Matrix Metalloproteinase-10 in Kidney Injury Repair and Disease.International journal of molecular sciences · 2022Review
- Molecular and Cellular Mechanisms Underlying the Initiation and Progression of Alport Glomerular Pathology.Frontiers in medicine · 2022Review
- Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Alport Syndrome: A Primer for Clinicians.International journal of molecular sciences · 2021Review
- LAMA2 and LOXL4 are candidate FSGS genes.BMC nephrology · 2021Article
- A deletion in the N-terminal polymerizing domain of laminin β2 is a new mouse model of chronic nephrotic syndrome.Kidney international · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
It has been known for some time that laminins containing α1 and α2 chains, which are normally restricted to the mesangial matrix, accumulate in the glomerular basement membranes (GBM) of Alport mice, dogs, and humans. We show that laminins containing the α2 chain, but not those containing the α1 chain activates focal adhesion kinase (FAK) on glomerular podocytes in vitro and in vivo. CD151-null mice, which have weakened podocyte adhesion to the GBM rendering these mice more susceptible to biomechanical strain in the glomerulus, also show progressive accumulation of α2 laminins in the GBM, and podocyte FAK activation. Analysis of glomerular mRNA from both models demonstrates significant induction of MMP-9, MMP-10, MMP-12, MMPs linked to GBM destruction in Alport disease models, as well as the pro-inflammatory cytokine IL-6. SiRNA knockdown of FAK in cultured podocytes significantly reduced expression of MMP-9, MMP-10 and IL-6, but not MMP-12. Treatment of Alport mice with TAE226, a small molecule inhibitor of FAK activation, ameliorated fibrosis and glomerulosclerosis, significantly reduced proteinuria and blood urea nitrogen levels, and partially restored GBM ultrastructure. Glomerular expression of MMP-9, MMP-10 and MMP-12 mRNAs was significantly reduced in TAE226 treated animals. Collectively, this work identifies laminin α2-mediated FAK activation in podocytes as an important early event in Alport glomerular pathogenesis and suggests that FAK inhibitors, if safe formulations can be developed, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages.
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.