ArticleJournal of the American Society of Nephrology : JASN2014
Hypoxia-inducible factor-1α causes renal cyst expansion through calcium-activated chloride secretion.
Article in Journal of the American Society of Nephrology : JASN, 2014. 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, 68 citations in OpenAlex.
- Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors.Nephrology (Carlton, Vic.) · 2021Guideline
- Myofibroblast- specific autophagy drives cyst growth in autosomal dominant polycystic kidney disease.Cell communication and signaling : CCS · 2026Article
- Attribute-based cross-classification reveals sex- and age-specific prognostic impact of anemia in ADPKD.Clinical and experimental nephrology · 2026Article
- HIF-Regulated Pannexin-1 Channel Drives Luminal ATP Accumulation in Kidney Cysts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- Association of anemia with long-term renal prognosis in autosomal dominant polycystic kidney disease using time-series analysis.Scientific reports · 2026Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Role in Cystogenesis and Novel Therapeutic Approaches.Biomedicines · 2025Review
- Targeting TRPM3 as a potential therapeutic approach for autosomal dominant polycystic kidney disease.Scientific reports · 2025Article
- The CLCA1/TMEM16A/Cl- current axis associates with H2S deficiency in diabetic kidney injury.JCI insight · 2025Article
- Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Article
- Defects of renal tubular homeostasis and cystogenesis in theiScience · 2024Article
- Inspiring Tactics with the Improvement of Mitophagy and Redox Balance for the Development of Innovative Treatment against Polycystic Kidney Disease.Biomolecules · 2024Review
- Hypoxia induces polycystin-1 expression in the renal epithelium.Royal Society open science · 2023Article
- Review
- Sodium-glucose cotransporter inhibition in polycystic kidney disease: fact or fiction.Clinical kidney journal · 2022Review
- Article
- Potential Therapeutic Effects of Long-Term Stem Cell Administration: Impact on the Gene Profile and Kidney Function of PKD/Mhm (Cy/+) Rats.Journal of clinical medicine · 2022Article
- Primary URECs: a source to better understand the pathology of renal tubular epithelia in pediatric hereditary cystic kidney diseases.Orphanet journal of rare diseases · 2022Article
- The chloride channel CFTR is not required for cyst growth in an ADPKD mouse model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polycystic kidney diseases are characterized by numerous bilateral renal cysts that continuously enlarge and, through compression of intact nephrons, lead to a decline in kidney function over time. We previously showed that cyst enlargement is accompanied by regional hypoxia, which results in the stabilization of hypoxia-inducible transcription factor-1α (HIF-1α) in the cyst epithelium. Here we demonstrate a correlation between cyst size and the expression of the HIF-1α-target gene, glucose transporter 1, and report that HIF-1α promotes renal cyst growth in two in vitro cyst models-principal-like MDCK cells (plMDCKs) within a collagen matrix and cultured embryonic mouse kidneys stimulated with forskolin. In both models, augmenting HIF-1α levels with the prolyl hydroxylase inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate enhanced cyst growth. In addition, inhibition of HIF-1α degradation through tubule-specific knockdown of the von Hippel-Lindau tumor suppressor increased cyst size in the embryonic kidney cyst model. In contrast, inhibition of HIF-1α by chetomin and knockdown of HIF-1α both decreased cyst growth in these models. Consistent with previous reports, plMDCK cyst enlargement was driven largely by transepithelial chloride secretion, which consists, in part, of a calcium-activated chloride conductance. plMDCKs deficient for HIF-1α almost completely lacked calcium-activated chloride secretion. We conclude that regional hypoxia in renal cysts contributes to cyst growth, primarily due to HIF-1α-dependent calcium-activated chloride secretion. These findings identify the HIF system as a novel target for inhibition of cyst growth.
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.