ArticleHypertension (Dallas, Tex. : 1979)2018
Klotho Ameliorates Medullary Fibrosis and Pressure Natriuresis in Hypertensive Rat Kidneys.
Article in Hypertension (Dallas, Tex. : 1979), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Comparative Diagnostic Performance of Serum α-Klotho and FGF-23 in Predicting Obstructive Sleep Apnea Severity: A Novel Biomarker Approach.Journal of clinical medicine · 2026Article
- Association between circulating Klotho levels and hypertension: insights from NHANES, Mendelian randomization, and an Asian cohort.Renal failure · 2025Article
- Adipokines and Vascular Modulators in CKM: Emerging Biomarkers as Diagnostic and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- Klotho protein: a new insight into the pathogenesis of essential hypertension.Clinical hypertension · 2024Article
- Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024Review
- Dietary High Salt Intake Exacerbates SGK1-Mediated T Cell Pathogenicity in L-NAME/High Salt-Induced Hypertension.International journal of molecular sciences · 2024Article
- New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms.Frontiers in immunology · 2024Review
- Hypertension and cellular senescence.Biogerontology · 2023Review
- Hydrogen Sulfide Inhibited Sympathetic Activation in D-Galactose-Induced Aging Rats by Upregulating Klotho and Inhibiting Inflammation in the Paraventricular Nucleus.Biomedicines · 2023Article
- Klotho Modulates Pro-Fibrotic Activities in Human Atrial Fibroblasts through Inhibition of Phospholipase C Signaling and Suppression of Store-Operated Calcium Entry.Biomedicines · 2022Article
- Low Serum Klotho Associated With All-cause Mortality Among a Nationally Representative Sample of American Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- EPA-Enriched Phospholipids Alleviate Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating TGF-β Signaling Pathways.Marine drugs · 2022Article
- Pathophysiology and genetics of salt-sensitive hypertension.Frontiers in physiology · 2022Review
- Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.Frontiers in aging · 2022Review
- The HIF-1α/p53/miRNA-34a/Klotho axis in retinal pigment epithelial cells promotes subretinal fibrosis and exacerbates choroidal neovascularization.Journal of cellular and molecular medicine · 2021Article
- Klotho: a link between cardiovascular and non-cardiovascular mortality.Clinical kidney journal · 2020Article
- Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats.Experimental and therapeutic medicine · 2020Article
- Endothelial prolyl hydroxylase 2 is necessary for angiotensin II-mediated renal fibrosis and injury.American journal of physiology. Renal physiology · 2020Article
- Fibroblast Growth Factor 23 and Blood Pressure in Older Adults: The Health, Aging, and Body Composition Study.Hypertension (Dallas, Tex. : 1979) · 2020Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Renal expression of klotho is reduced in hypertension. Experiments were performed to examine whether exogenous klotho protein supplementation ameliorates pressure natriuresis in early phase of hypertension, using stroke-prone spontaneously hypertensive rats (sp-SHR). The interactions between klotho protein and renal renin-Ang (angiotensin) system were examined with immunoprecipitation and cell culture methods. Uninephrectomy was performed in sp-SHRs to induce nephrosclerosis, and they were treated with exogenous klotho protein or vehicle. Exogenous klotho protein supplementation to sp-SHR decreased blood pressure, renal Ang II levels, AGT (angiotensinogen) expression, HIF (hypoxia-inducible factor)-1α abundance, and medullary fibronectin levels, with increased renal klotho expression and serum and urine klotho levels. Klotho supplementation also reduced kidney weight, renal phosphorylated Akt, and mTOR (mammalian target of rapamycin) abundance. Furthermore, klotho supplementation restored renal autoregulation of glomerular filtration rate and enhanced pressure-induced natriuresis in sp-SHR. Klotho protein bound to AT1R (Ang II type-1 receptor) and decreased the presence of AT1R on HK-2 (human proximal tubular) cells, attenuating inositol triphosphate generation. Klotho protein suppressed Ang II-induced increments of AGT expression in HK-2 cells. Collectively, the present data demonstrate that klotho binds with the AT1R to suppress Ang signal transduction, participating in inactivating renal renin-Ang system. Our results also suggest that exogenous klotho supplementation represses Akt-mTOR signaling to reduce renal hypertrophy and restore the autoregulatory ability of glomerular filtration rate in uninephrectomized sp-SHRs. Finally, the present findings implicate that klotho supplementation inhibits HIF-1α pathway and medullary fibrosis, contributing to enhancements of pressure natriuresis and reduction in blood pressure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.