Evidence map›Paper›PMID 38912583›Full record

ArticleJCI insight2024

Reduced decay-accelerating factor expression promotes complement-mediated cystogenesis in murine ADPKD.

Sofia Bin, Miran Yoo, Paolo Molinari, Micaela Gentile, Kelly Budge, Chiara Cantarelli, Yaseen Khan, Gaetano La Manna, William M Baldwin, Nina Dvorina and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Sofia BinTranslational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Miran YooDivision of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Paolo MolinariTranslational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Micaela GentileTranslational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kelly BudgeTranslational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Chiara CantarelliUnità Operativa Nefrologia, Azienda-Ospedaliero University of Parma, Department of Medicine and Syrgery, University of Parma, Italy.
Yaseen KhanTranslational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Gaetano La MannaNephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero- University of Bologna, Italy.
William M BaldwinDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Nina DvorinaDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Paolo CravediTranslational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
G Luca GusellaDivision of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Funding

National Coordinating Center (NCC) for the Polycystic Kidney Disease (PKD) Research and Translation Core CentersU24DK126110 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI Terry J Watnick · 2020 to 2026
$7.4M
Biomechanical drivers of cystogenesisR01DK131047 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AZELOGLU, EVREN U., GUSELLA, GABRIELE LUCA · 2021 to 2024
$2.7M
NIDDK NIH HHS R01 DK131047NIDDK NIH HHS U24 DK126110
6 · The paper itself

Abstract

Patients with autosomal dominant polycystic kidney disease (ADPKD), a genetic disease due to mutations of the PKD1 or PKD2 gene, show signs of complement activation in the urine and cystic fluid, but their pathogenic role in cystogenesis is unclear. We tested the causal relationship between complement activation and cyst growth using a Pkd1KO renal tubular cell line and newly generated conditional Pkd1-/- C3-/- mice. Pkd1-deficient tubular cells have increased expression of complement-related genes (C3, C5, CfB, C3ar, and C5ar1), while the gene and protein expression of complement regulators DAF, CD59, and Crry is decreased. Pkd1-/- C3-/- mice are unable to fully activate the complement cascade and are characterized by a significantly slower kidney cystogenesis, preserved renal function, and reduced intrarenal inflammation compared with Pkd1-/- C3+/+ controls. Transgenic expression of the cytoplasmic C-terminal tail of Pkd1 in Pkd1KO cells lowered C5ar1 expression, restored Daf levels, and reduced cell proliferation. Consistently, both DAF overexpression and pharmacological inhibition of C5aR1 (but not C3aR) reduced Pkd1KO cell proliferation. In conclusion, the loss of Pkd1 promotes unleashed activation of locally produced complement by downregulating DAF expression in renal tubular cells. Increased C5a formation and C5aR1 activation in tubular cells promotes cyst growth, offering a new therapeutic target.

Indexed as

CD55 AntigensComplement C3Mice, KnockoutPolycystic Kidney, Autosomal DominantAnimalsCell LineCell ProliferationComplement ActivationDisease Models, AnimalHumansMaleMiceReceptor, Anaphylatoxin C5aReceptors, Complement 3bTRPP Cation ChannelsC3 protein, mouseC5ar1 protein, mouseCD55 AntigensComplement C3Cr1l protein, mouseReceptor, Anaphylatoxin C5aReceptors, Complement 3bTRPP Cation ChannelsComplementNephrology

Identifiers

PMID38912583
PMCPMC11383362

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.