---
title: "ETV Transcription Factors and Hedgehog Signaling in Renal Cyst Initiation and Progression"
id: "biorxiv-4-mechanism-of-renal-cyst-initiation-and-progression-through-etv-transcription"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-4-mechanism-of-renal-cyst-initiation-and-progression-through-etv-transcription"
content_type: "clinical_feed_article"
specialty: "Nephrology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.21.746191v1?rss=1"
published_at: "2026-08-26T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# ETV Transcription Factors and Hedgehog Signaling in Renal Cyst Initiation and Progression
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-4-mechanism-of-renal-cyst-initiation-and-progression-through-etv-transcription
- **Specialty:** [Nephrology](https://medichelpline.com/clinical-feed/nephrology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.21.746191v1?rss=1)
- **Published At:** 2026-08-26T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study used genetic mutation models targeting the **ETV** family of transcription factors—**ETV1**, **ETV4**, and **ETV5**—and a pharmacological hedgehog pathway inhibitor, cyclopamine, to study mechanisms of renal cyst formation and growth. - Renal cyst biology was parsed into two phases: **cyst initiation** and **cyst progression/promotion**, recognizing that pathogenic cysts arise from repeated initiation followed by growth. - Nephron-specific deletion of **ETV4** and **ETV5** triggered initial cyst formation, indicating these factors constrain early cyst initiation in the kidney. - Despite initial cyst formation after ETV4/ETV5 deletion, most early cysts did not continue to grow during animal maturation; only a limited subset progressed further without additional perturbation. - Additional deletion of **ETV1** was required to produce ongoing, continuous cyst initiation and to promote further cyst growth, implicating combined loss of ETV factors in sustained pathogenic cyst development. - Pharmacologic blockade of **hedgehog signaling** with cyclopamine reduced the promotion of cyst progression but had minimal effect on the initial formation of cysts, suggesting hedgehog activity drives growth rather than initiation. - The data support that **cyst initiation and cyst progression are genetically and molecularly distinct** processes that can be separately modulated by transcription factor status and hedgehog pathway activity. - These findings imply potential strategies to suppress pathogenic renal cyst growth by targeting progression-promoting pathways while recognizing initiation may require different interventions. - The report is a preprint posted on bioRxiv (August 26, 2026) by Borum Ryu, Ligyeom Ha, Del L Dsouza, Erika I Boesen, and Sung-Ho Huh; authors declared no competing interests.
## Clinical Analysis & Structured Key Points
Mechanism of Renal Cyst Initiation and Progression Through ETV Transcription Factors and Hedgehog Signaling | bioRxiv Skip to main content New Results Mechanism of Renal Cyst Initiation and Progression Through ETV Transcription Factors and Hedgehog Signaling View ORCID Profile Borum Ryu , Ligyeom Ha , View ORCID Profile Del L Dsouza , View ORCID Profile Erika I Boesen , View ORCID Profile Sung-Ho Huh doi: https://doi.org/10.64898/2026.08.21.746191 Borum Ryu 1 UMMC: University of Maryland Medical Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Borum Ryu Ligyeom Ha 2 UNMC: University of Nebraska Medical Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Del L Dsouza 2 UNMC: University of Nebraska Medical Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Del L Dsouza Erika I Boesen 2 UNMC: University of Nebraska Medical Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Erika I Boesen Sung-Ho Huh 3 UMMC: The University of Mississippi Medical Center Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sung-Ho Huh For correspondence: shuh{at}umc.edu Abstract Info/History Metrics Preview PDF Abstract Renal cysts are categorized as non-pathogenic simple cysts and pathogenic malignant cysts based on their pathophysiological status. Cyst formation is divided by cyst initiation and cyst progression/promotion. Pathogenic cysts are thought to be developed through continuous initiation followed by progression until pathogenic status is achieved. Although many genetic and environmental factors are identified to cause pathogenic cyst formation, the mechanisms that discriminate cyst initiation and progression are poorly understood. Using genetic mutation models of ETV transcription factors, ETV1, ETV4, and ETV5, and a pharmacological inhibitor of hedgehog signaling, cyclopamine, we identified one of the mechanisms regulating cyst initiation and progression. Nephron specific deletion of ETV4 and ETV5 initiated cyst formation. However, cyst initiation did not continue as animals grow, and a limited number of the initial cysts underwent further growth. Additional deletion of ETV1 was required for continuous initiation in addition to promotion of cyst growth. Furthermore, administration of cyclopamine attenuated promotion of cyst progression but had little effect on cyst initiation. Therefore, we provide evidence that cyst initiation and progression is genetically and molecularly distinct and can be modulated. This information provides new insight into how to control renal cyst initiation and progression and can be used to suppress pathogenic cyst growth. Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted August 26, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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Share Mechanism of Renal Cyst Initiation and Progression Through ETV Transcription Factors and Hedgehog Signaling Borum Ryu , Ligyeom Ha , Del L Dsouza , Erika I Boesen , Sung-Ho Huh bioRxiv 2026.08.21.746191; doi: https://doi.org/10.64898/2026.08.21.746191 Share This Article: Copy Citation Tools Mechanism of Renal Cyst Initiation and Progression Through ETV Transcription Factors and Hedgehog Signaling Borum Ryu , Ligyeom Ha , Del L Dsouza , Erika I Boesen , Sung-Ho Huh bioRxiv 2026.08.21.746191; doi: https://doi.org/10.64898/2026.08.21.746191 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (7930) Biochemistry (18537) Bioengineering (14698) Bioinformatics (43911) Biophysics (22338) Cancer Biology (19460) Cell Biology (26629) Clinical Trials (138) Developmental Biology (13844) Ecology (20766) Epidemiology (2067) Evolutionary Biology (25201) Genetics (16043) Genomics (23310) Immunology (18498) Microbiology (42020) Molecular Biology (17858) Neuroscience (92410) Paleontology (691) Pathology (2951) Pharmacology and Toxicology (5044) Physiology (8023) Plant Biology (15810) Scientific Communication and Education (2089) Synthetic Biology (4514) Systems Biology (10144) Zoology (2367)
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