ArticleScientific reports2016
Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Urinary Proteomics Identifies Cathepsin D as a Biomarker of Rapid eGFR Decline in Type 1 Diabetes.Diabetes care · 2022Pooled it
- Effects of finerenone on arterial stiffness and cardiorenal biomarkers in patients with type 2 diabetes and chronic kidney disease: a randomised placebo-controlled mechanistic trial (FIVE-STAR).Cardiovascular diabetology · 2025Trial
- Trial
- Quercetin Ameliorates Skeletal Muscle Fibrosis After Injury by Interfering with Macrophage-Myofibroblast Transition.Journal of inflammation research · 2026Article
- Proteomics of Urinary Extracellular Vesicles Highlight the Involvement of Vitronectin and the Fibrinolytic and TNF Pathways as Mechanisms Underlying Renal Fibrosis in Kidney Transplant Patients.Journal of extracellular biology · 2025Article
- Article
- Fluorofenidone attenuates renal fibrosis by inhibiting lysosomal cathepsin‑mediated NLRP3 inflammasome activation.Experimental and therapeutic medicine · 2024Article
- Review
- Cathepsin D elevates the fibrocalcific activity in human aortic valve cells through the ERK1/2-Sox9 pathway.Frontiers in cardiovascular medicine · 2024Article
- Urine proteomics by mass spectrometry identifies proteins involved in key pathogenic pathways in patients with juvenile dermatomyositis.Rheumatology (Oxford, England) · 2023Article
- Plk1 promotes renal tubulointerstitial fibrosis by targeting autophagy/lysosome axis.Cell death & disease · 2023Article
- Loss of cystatin C regulates permeability and inflammatory pathways in retina.Microvascular research · 2023Article
- Multi‑faceted roles of cathepsins in ischemia reperfusion injury (Review).Molecular medicine reports · 2022Review
- lncRNA TUG1 regulates hyperuricemia-induced renal fibrosis in a rat model.Acta biochimica et biophysica Sinica · 2022Article
- Low-dose chloroquine treatment extends the lifespan of aged rats.Protein & cell · 2022Article
- Hormonal Regulation of Renal Fibrosis.Life (Basel, Switzerland) · 2022Review
- Therapeutic Implications of Ferroptosis in Renal Fibrosis.Frontiers in molecular biosciences · 2022Review
- A Novel Urinary Proteomics Classifier for Non-Invasive Evaluation of Interstitial Fibrosis and Tubular Atrophy in Chronic Kidney Disease.Proteomes · 2021Article
- Expression of Cathepsins B, D, and G in Extracranial Arterio-Venous Malformation.Frontiers in surgery · 2021Article
- Proteolytic cleavage of Podocin by Matriptase exacerbates podocyte injury.The Journal of biological chemistry · 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
11 authors at 4 institutions in 3 countries.
Funding
Abstract
During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for cathepsins in CKD. CtsD and B were located in distal and proximal tubular cells respectively in human disease. Administration of CtsD (Pepstatin A) but not B inhibitor (Ca074-Me), in two mouse CKD models, UUO and chronic ischemia reperfusion injury, led to a reduction in fibrosis. No changes in collagen transcription or myofibroblasts numbers were observed. Pepstatin A administration resulted in increased extracellular urokinase and collagen degradation. In vitro and in vivo administration of chloroquine, an endo/lysosomal inhibitor, mimicked Pepstatin A effect on renal fibrosis. Therefore, we propose a mechanism by which CtsD inhibition leads to increased collagenolytic activity due to an impairment in lysosomal recycling. This results in increased extracellular activity of enzymes such as urokinase, triggering a proteolytic cascade, which culminates in more ECM degradation. Taken together these results suggest that inhibition of lysosomal proteases, such as CtsD, could be a new therapeutic approach to reduce renal fibrosis and slow progression of CKD.
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.