Transcriptomics

Dataset Information

0

Chondroitin sulfate N-acetylgalactosaminyltransferase 1 promotes the progression of renal fibrosis mediated by versican 1 in mouse remnant kidney


ABSTRACT: Aim: Renal fibrosis is a final common pathway for progressive chronic kidney diseases. Immune cell infiltration and production of tumor growth factor-β (TGF-β) are essential factors for fibrosis development. We examined the role of chondroitin sulfate (CS) proteoglycan, which is one of the main extracellular matrix components induced by TGF-β signaling. We also examined CS N-acetylgalactosaminyltransferase 1 (T1), an enzyme that catalyzes the first step of CS-specific synthesis. Methods: T1-/- mice, genetically lacking T1, and T1+/+ mice underwent 5/6 nephrectomy (Nx) or sham operation. Kidney function, urine marker, mRNA expression, and TGF-β signaling were evaluated 1 month after Nx or sham operation. Renal fibrotic area was quantified 3 months later. Results: Both T1+/+ and T1-/- mice with Nx showed equivalent loss of kidney function, however, a tubular damage marker, upregulation of TGF-β and collagen expression, and renal fibrosis were suppressed in T1-/- mice with Nx. Versican, one of the core proteins of CS proteoglycan, was exclusively upregulated in T1+/+ mice with Nx. Among the versican splicing variants, versican 1 (V1) was expressed in the medullary interstitium of the remnant kidney in T1+/+ mice. V1 was produced in the interstitial macrophages, fibroblasts/myofibroblasts, and endothelial cells, whereas TGF-β was expressed in endothelial cells. Phosphorylation of the TGF-β signaling molecules Smad2/3 was not induced in T1-/- mice with Nx. In vivo administration of TGF-β inhibitor into Nx mice reduced V1 and Tgfb expression. Conclusion: T1 was essential for the initial induction of V1 upregulation, effective TGF-β signaling, and subsequent renal fibrosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE292187 | GEO | 2025/03/23

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-10-01 | GSE242295 | GEO
2022-09-23 | PXD025456 | Pride
2018-08-08 | GSE54441 | GEO
2024-06-03 | PXD052293 | Pride
2024-06-03 | PXD052244 | Pride
2023-11-01 | GSE218814 | GEO
2024-09-30 | GSE270531 | GEO
2022-02-16 | PXD021357 | Pride
2022-07-19 | GSE203063 | GEO
2017-08-12 | GSE100632 | GEO