Tuberous Sclerosis Complex Kidney Lesion Pathogenesis: A Developmental Perspective.
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
01 07 2023
01 07 2023
Historique:
received:
04
10
2022
accepted:
27
03
2023
pmc-release:
01
07
2024
medline:
5
7
2023
pubmed:
16
4
2023
entrez:
15
4
2023
Statut:
ppublish
Résumé
The phenotypic diversity of tuberous sclerosis complex (TSC) kidney pathology is enigmatic. Despite a well-established monogenic etiology, an incomplete understanding of lesion pathogenesis persists. In this review, we explore the question: How do TSC kidney lesions arise? We appraise literature findings in the context of mutational timing and cell-of-origin. Through a developmental lens, we integrate the critical results from clinical studies, human specimens, and genetic animal models. We also review novel insights gleaned from emerging organoid and single-cell sequencing technologies. We present a new model of pathogenesis which posits a phenotypic continuum, whereby lesions arise by mutagenesis during development from variably timed second-hit events. This model can serve as a conceptual framework for testing hypotheses of TSC lesion pathogenesis, both in the kidney and in other affected tissues.
Identifiants
pubmed: 37060140
doi: 10.1681/ASN.0000000000000146
pii: 00001751-202307000-00005
pmc: PMC10356159
doi:
Substances chimiques
Tumor Suppressor Proteins
0
Tuberous Sclerosis Complex 2 Protein
0
Tuberous Sclerosis Complex 1 Protein
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1135-1149Subventions
Organisme : CIHR
ID : FRN-153188
Pays : Canada
Informations de copyright
Copyright © 2023 by the American Society of Nephrology.
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