Collagen fibrils and cell nuclei are entrapped within Randall's plaques but not in <scp>CaOx</scp> matrix overgrowth: A microscopic inquiry into Randall's plaque stone pathogenesis

Canela, Victor Hugo; Bledsoe, Sharon B.; Worcester, Elaine M.; Lingeman, James E.; El‐Achkar, Tarek M.; Williams, James C.

doi:10.1002/ar.24837

Cited by 2 publications

(2 citation statements)

References 43 publications

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“…This finding agrees with the matrix remodeling transcriptomic signature observed, which frequently results from chronic non-resolving inflammation. This is also consistent with recent findings by Canela et al showing fibrosis and immune signature derived from imaging of CaOx stones with RP (Canela et al 2021).…”

Section: Discussionsupporting

confidence: 93%

A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury and matrix remodeling in patients with stone disease

Canela

Bowen

Ferreira

et al. 2022

Preprint

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Kidney stone disease causes significant morbidity and increases health care utilization. The pathogenesis of stone disease is not completely understood, due in part to the poor characterization of the cellular and molecular makeup of the kidney papilla and its alteration with disease. We deciphered the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease compared to healthy subjects using single nuclear RNA sequencing, spatial transcriptomics and high-resolution large-scale multiplexed 3D and Co-Detection by indexing (CODEX) imaging. In addition to identifying cell types important in papillary physiology, we defined subtypes of immune, stromal and principal cells enriched in the papilla, and characterized an undifferentiated epithelial cell cluster that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncovered a global injury signature involving multiple cell types within the papilla, characterized by immune activation, oxidative stress and extracellular matrix remodeling. The microenvironment of mineral deposition had features of an immune synapse with antigen presenting inflammatory macrophages interacting with T cells, and an immune repertoire ranging from inflammation to fibrosis. The expression of MMP7 and MMP9 was associated with stone disease and mineral deposition, respectively. MMP7 and MMP9 were significantly increased in the urine of patients with CaOx stone disease compared to non-stone formers, and their levels correlated with disease activity in stone formers. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla, and identify potential urinary biomarkers.

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Section: Discussionsupporting

confidence: 93%

A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury and matrix remodeling in patients with stone disease

Canela

Bowen

Ferreira

et al. 2022

Preprint

Self Cite

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“…The formation of calcium oxalate (CaOx) kidney stones is related to the deposition of calcium phosphate on the renal papillae. , Various calcium phosphate salts, such as calcium phosphate (CaP), amorphous calcium phosphate, and hydroxyapatite (HAP), are present in urine. − These salts can be used as crystal nests to induce the formation of CaOx stones. , …”

Section: Introductionmentioning

confidence: 99%

Size-Dependent Cytotoxicity, Adhesion, and Endocytosis of Micro-/Nano-hydroxyapatite Crystals in HK-2 Cells

Han,

Tong,

Rao

et al. 2023

ACS Omega

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Nano-hydroxyapatite (nano-HAP) is often used as a crystal nest to induce calcium oxalate (CaOx) kidney stone formation, but the mechanism of interaction between HAP crystals of different properties and renal tubular epithelial cells remains unclear. In this study, the adhesion and endocytosis of HAP crystals with sizes of 40 nm, 70 nm, 1 μm, and 2 μm (HAP-40 nm, HAP-70 nm, HAP-1 μm, and HAP-2 μm, respectively) to human renal proximal tubular epithelial cells (HK-2) were comparatively studied. The results showed that HAP crystals of all sizes promoted the expression of osteopontin and hyaluronic acid on the cell surface, destroyed the integrity of the lysosomes, and induced the apoptosis and necrosis of cells. Nano-HAP crystals had a higher specific surface area, a smaller contact angle, a higher surface energy, and a lower Zeta potential than those of micro-HAP. Therefore, the abilities of HK-2 cells to adhere to and endocytose nano-HAP crystals were greater than their abilities to do the same for micro-HAP crystals. The order of the endocytosed crystals was as follows: HAP-40 nm > HAP-70 nm > HAP-1 μm > HAP-2 μm. The endocytosed HAP crystals entered the lysosomes. The more crystal endocytosis and adhesion there is, the more toxic it is to HK-2 cells. The results of this study showed that nanosized HAP crystals greatly promoted the formation of kidney stones than micrometer-sized HAP crystals.

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Collagen fibrils and cell nuclei are entrapped within Randall's plaques but not in CaOx matrix overgrowth: A microscopic inquiry into Randall's plaque stone pathogenesis

Cited by 2 publications

References 43 publications

A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury and matrix remodeling in patients with stone disease

A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury and matrix remodeling in patients with stone disease

Size-Dependent Cytotoxicity, Adhesion, and Endocytosis of Micro-/Nano-hydroxyapatite Crystals in HK-2 Cells

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