Upregulation of Piezo2 in the mesangial, renin, and perivascular mesenchymal cells of the kidney of Dahl salt-sensitive hypertensive rats and its reversal by esaxerenone

Ochiai, Koji; Mochida, Yuki; Nagase, Takeshi; Fukuhara, Hiroshi; Yamaguchi, Yoshihiro; Nagase, Miki

doi:10.1038/s41440-023-01219-9

Cited by 8 publications

(4 citation statements)

References 52 publications

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“…Although the OR10G6 gene is related to the olfactory system, its variant rs1453654 was associated with the elevated expression of IFNγ after smallpox vaccination [61]. In a rat model of hypertension disease, Piezo2 activation was observed in mesangial cells, renin cells, and perivascular mesenchymal cells, implying its contribution to renal fibrosis [62]. Based on the dominant model, we identified the ITGAM gene among the IgAN candidate genes with repeatedly confirmed association [63].…”

Section: Discussionmentioning

confidence: 69%

Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study

Buianova,

Proskura,

Cheranev

et al. 2023

IJMS

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IgA nephropathy (IgAN) is an autoimmune disorder which is believed to be non-monogenic. We performed an exome-wide association study of 70 children with IgAN and 637 healthy donors. The HLA allele frequencies were compared between the patients and healthy donors from the bone marrow registry of the Pirogov University. We tested 78,020 gene markers for association and performed functional enrichment analysis and transcription factor binding preference detection. We identified 333 genetic variants, employing three inheritance models. The most significant association with the disorder was observed for rs143409664 (PRAG1) in the case of the additive and dominant models (PBONF = 1.808 × 10−15 and PBONF = 1.654 × 10−15, respectively), and for rs13028230 (UBR3) in the case of the recessive model (PBONF = 1.545 × 10−9). Enrichment analysis indicated the strongly overrepresented “immune system” and “kidney development” terms. The HLA-DQA1*01:01:01G allele (p = 0.0076; OR, 2.021 [95% CI, 1.322–3.048]) was significantly the most frequent among IgAN patients. Here, we characterized, for the first time, the genetic background of Russian IgAN patients, identifying the risk alleles typical of the population. The most important signals were detected in previously undescribed loci.

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Section: Discussionmentioning

confidence: 69%

Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study

Buianova,

Proskura,

Cheranev

et al. 2023

IJMS

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“…To establish the expression patterns of PIEZOs in the mouse kidney, we first examined the localization of mRNA transcripts of mechanosensory PIEZO channels using single molecule fluorescence in situ hybridization (smFISH). We found that Piezo2 and not Piezo1 was expressed in Ren1-expressing JG cells of the JGA and in Pdgfrb-expressing mesangial cells of the glomerulus 32,33 (Fig. 1a-c).…”

Section: Piezo2 Is Expressed In Juxtaglomerular and Mesangial Cells O...mentioning

confidence: 86%

Renal mechanotransduction is an essential regulator of renin

Hill,

Shirvan,

Burquez

et al. 2023

Preprint

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The kidneys tightly control the composition of our internal environment to maintain homeostasis in the face of external variability. The regulation of blood volume begins in the kidneys and is essential for vertebrate life in terrestrial environments where salt and water availability are unpredictable1,2. Renin synthesis and release by juxtaglomerular granular cells of the kidney is the rate-limiting step in a hormonal cascade that modulates blood volume, filtration, and salt balance2. Renin is stimulated during hypovolemia and salt deprivation in response to chemical cues released from sympathetic efferent neurons and the macula densa onto the juxtaglomerular granular cells. Renin levels are also proposed to be modulated by mechanical forces elicited by changes in blood volume and/or pressure exerted upon juxtaglomerular cells2–4. However, the identity and significance of the juxtaglomerular mechanotransducer(s) was unknown. We found that the force-gated ion channel PIEZO2 is expressed in juxtaglomerular granular cells and in neighboring mesangial cells. Selective genetic ablation of PIEZO2 dysregulated the renin-angiotensin-aldosterone system by elevating renin, raising systemic blood pressure, inducing glomerular hyperfiltration, and exaggerating the hormonal response to volume depletion. These findings demonstrate that PIEZO2 contributes to renal blood volume sensing and kidney functionin vivo.

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“…[133][134][135] In addition, research by Mochida Y et al has demonstrated that Piezo2 expression decreased in mesangial cells after dehydration, which is likely due to intraglomerular hypotension induced by dehydration. 132 A subsequent study by the same group showed that Piezo2 expression was enhanced in proliferated and hypertrophic mesangial cells and Ren 1-positive cells in high-salt-fed Dahl rats, which was associated with hypertension and nephrosclerosis 136 (Table 4). This finding links the Piezo channel with glomerulosclerosis.…”

Section: Podocytes and Mesangial Cellsmentioning

confidence: 95%

Mechanosensing by Piezo1 and its implications in the kidney

Yuan,

Zhao,

Wang

et al. 2024

Acta Physiologica

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Piezo1 is an essential mechanosensitive transduction ion channel in mammals. Its unique structure makes it capable of converting mechanical cues into electrical and biological signals, modulating biological and (patho)physiological processes in a wide variety of cells. There is increasing evidence demonstrating that the piezo1 channel plays a vital role in renal physiology and disease conditions. This review summarizes the current evidence on the structure and properties of Piezo1, gating modulation, and pharmacological characteristics, with special focus on the distribution and (patho)physiological significance of Piezo1 in the kidney, which may provide insights into potential treatment targets for renal diseases involving this ion channel.

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Upregulation of Piezo2 in the mesangial, renin, and perivascular mesenchymal cells of the kidney of Dahl salt-sensitive hypertensive rats and its reversal by esaxerenone

Cited by 8 publications

References 52 publications

Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study

Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study

Renal mechanotransduction is an essential regulator of renin

Mechanosensing by Piezo1 and its implications in the kidney

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