Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport Nephropathy Article Swipe
Joon‐Ho Yoon
,
Zhenan Liu
,
Mathew O. Alaba
,
Leslie A. Bruggeman
,
Paul A. Janmey
,
C. Arana
,
Oluwatoyosi Ayenuyo
,
Isabela Novais Medeiros
,
Sean Eddy
,
Matthias Kretzler
,
Joel Henderson
,
Viji Nair
,
Abhijit S. Naik
,
Audrey N. Chang
,
R. Tyler Miller
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.02.26.582201
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.02.26.582201
To understand the early stages of Alport nephropathy, we characterize the structural, functional, and biophysical properties of glomerular capillaries and podocytes in Col4α3 -/- mice, analyze kidney cortex transcriptional profiles over time, and investigate the effects of the ER stress mitigation by TUDCA. We use human FSGS-associated genes (NEPTUNE) to identify common molecular pathways rescued by TUDCA in human glomerular disease and the Alport mouse model. In Col4α3 -/- mice, podocyte injury is evident by 3 months, with 40% podocyte loss and maximum deformability of glomeruli at 4 months, followed from months 4 to 7 by progressive capillary stiffening, increasing proteinuria, reduced renal function, inflammatory infiltrates, and fibrosis. Evidence of ER stress progresses over this timeframe. Glomerular and renal disease in Col4α3 -/- mice are suppressed by TUDCA. RNA sequencing at 2, 4, and 7 months reveals an injury-associated gene expression pattern shared by FSGS patients. Deconvolution analysis identified podocyte-associated FSGS gene set that when projected onto 4-month Col4α3 -/- mouse data was characteristic of hypertrophy, differentiation, and cytoskeleton/adhesion signals. Disease-associated changes in RNAs suppressed by TUDCA in Col4α3 -/- mice. We define two phases of Col4α3 -/- nephropathy. The first is characterized by podocytopathy and accelerated podocyte loss, while the second is marked by increased capillary wall stiffening, activation of renal inflammatory and profibrotic pathways, and loss of renal function. Characterization of the effects of TUDCA on Col4α3 -/- -induced glomerular and renal gene expression and the relation of these genes to human data identifies potential therapeutic targets in Alport and related nephropathies.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.02.26.582201
- https://www.biorxiv.org/content/biorxiv/early/2024/05/17/2024.02.26.582201.full.pdf
- OA Status
- green
- Cited By
- 3
- References
- 68
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4396714429
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4396714429Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2024.02.26.582201Digital Object Identifier
- Title
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Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport NephropathyWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-02-29Full publication date if available
- Authors
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Joon‐Ho Yoon, Zhenan Liu, Mathew O. Alaba, Leslie A. Bruggeman, Paul A. Janmey, C. Arana, Oluwatoyosi Ayenuyo, Isabela Novais Medeiros, Sean Eddy, Matthias Kretzler, Joel Henderson, Viji Nair, Abhijit S. Naik, Audrey N. Chang, R. Tyler MillerList of authors in order
- Landing page
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https://doi.org/10.1101/2024.02.26.582201Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2024/05/17/2024.02.26.582201.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2024/05/17/2024.02.26.582201.full.pdfDirect OA link when available
- Concepts
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Alport syndrome, Nephropathy, Gene, Elasticity (physics), Biology, Glomerulonephritis, Genetics, Endocrinology, Diabetes mellitus, Kidney, Materials science, Composite materialTop concepts (fields/topics) attached by OpenAlex
- Cited by
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3Total citation count in OpenAlex
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2025: 3Per-year citation counts (last 5 years)
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68Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.structural, | 12 |
| abstract_inverted_index.therapeutic | 248 |
| abstract_inverted_index.characterize | 10 |
| abstract_inverted_index.hypertrophy, | 166 |
| abstract_inverted_index.infiltrates, | 106 |
| abstract_inverted_index.inflammatory | 105, 213 |
| abstract_inverted_index.nephropathy, | 8 |
| abstract_inverted_index.nephropathy. | 189 |
| abstract_inverted_index.proteinuria, | 101 |
| abstract_inverted_index.Deconvolution | 147 |
| abstract_inverted_index.characterized | 193 |
| abstract_inverted_index.deformability | 84 |
| abstract_inverted_index.podocytopathy | 195 |
| abstract_inverted_index.characteristic | 164 |
| abstract_inverted_index.nephropathies. | 254 |
| abstract_inverted_index.FSGS-associated | 47 |
| abstract_inverted_index.transcriptional | 29 |
| abstract_inverted_index.Characterization | 222 |
| abstract_inverted_index.differentiation, | 167 |
| abstract_inverted_index.injury-associated | 139 |
| abstract_inverted_index.Disease-associated | 171 |
| abstract_inverted_index.podocyte-associated | 150 |
| abstract_inverted_index.cytoskeleton/adhesion | 169 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 96 |
| corresponding_author_ids | https://openalex.org/A5033861833 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 15 |
| corresponding_institution_ids | https://openalex.org/I4210104138, https://openalex.org/I867280407 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7900000214576721 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.81415689 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |