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Klotho protein supplementation reduces blood pressure and renal hypertrophy in db/db mice, a model of type 2 diabetes.
Klotho interacts with various membrane proteins, such as receptors for transforming growth factor (TGF)-β and insulin-like growth factor (IGF), to alter their function. Renal expression of klotho is diminished in diabetes. The present study examined whether exogenous klotho protein supplementation ameliorates kidney injury and renin-angiotensin system (RAS) in db/db mice.
We investigated the effects of klotho supplementation on diabetic kidney injury and RAS. Recombinant human klotho protein (10 μg/kg/d) was administered to db/db mice daily.
Klotho protein supplementation reduced kidney weight, systolic blood pressure (SBP), albuminuria, glomerular filtration rate, and 8-epi-prostaglandin F2α excretion without affecting body weight. Although klotho supplementation did not alter glycated albumin, it reduced renal angiotensin II levels associated with reduced renal expression of angiotensinogen. Klotho supplementation improved renal expression of superoxide dismutase (SOD), and endogenous renal expression of klotho. Klotho supplementation reduced the levels of hypoxia-inducible factor, phosphorylated Akt, and phosphorylated mTOR and decreased the renal expression of TGF-β, tumour necrosis factor (TNF), and fibronectin.
These data indicate that klotho supplementation reduces blood pressure and albuminuria along with ameliorating renal RAS activation in db/db mice. Furthermore, these results suggest that klotho inhibits IGF signalling, induces SOD expression to reduce oxidative stress, and suppresses Akt-mTOR signalling to inhibit abnormal kidney growth. Collectively, the results suggest that klotho inhibits TGF-β and TNF signalling, resulting in a decline in renal fibrosis.
© 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
epithelial-mesenchymal transition; insulin-like growth factor; mTOR; superoxide dismutase; transforming growth factor; tumour necrosis factor
Bioelectronic Approaches to Control Neuroimmune Interactions in Acute Kidney Injury
Recent studies have shown renal protective effects of bioelectric approaches, including ultrasound treatment, electrical vagus nerve stimulation, and optogenetic brainstem C1 neuron stimulation. The renal protection acquired by all three modalities was lost in splenectomized mice and/or α7 subunit of the nicotinic acetylcholine receptor–deficient mice. C1 neuron-mediated renal protection was blocked by β2-adrenergic receptor antagonist. These findings indicate that all three methods commonly, at least partially, activate the cholinergic anti-inflammatory pathway, a well-studied neuroimmune pathway. In this article, we summarize the current understanding of neuroimmune axis-mediated kidney protection in preclinical models of acute kidney injury by these three modalities. Examination of the differences among these three modalities might lead to a further elucidation of the neuroimmune axis involved in renal protection and is of interest for developing new therapeutic approaches.
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Recombinant α-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy https://www.kidney-international.org/article/S0085-2538(16)30649-4/fulltext
Klotho to Treat Kidney Fibrosis https://jasn.asnjournals.org/content/24/5/687
Klotho: Therapeutic Agent for Ischemia Reperfusion Induced Acute Kidney Injury https://grantome.com/grant/NIH/R01-DK092461-04
Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury http://www.kjim.org/journal/view.php?number=169451
Klotho deficiency aggravates sepsis-related multiple organ dysfunction https://journals.physiology.org/doi/full/10.1152/ajprenal.00625.2017%40apsselect.2019.6.issue-2
Serum Klotho Levels in Trained Athletes https://sites.kowsarpub.com/num/articles/17236.html
Fibroblast growth factor-23 and Klotho in chronic kidney disease https://www.kisupplements.org/article/S2157-1716(15)31028-5/fulltext
Regulation of Blood Pressure by Klotho University of Oklahoma Health Sciences Center, Oklahoma City, OK, United Stateshttps://grantome.com/grant/NIH/R01-HL102074-01A1
KLOTHO SUPPLEMENTATION ATTENUATES BLOOD PRESSURE AND OXIDATIVE STRESS IN DIABETES https://journals.lww.com/jhypertension/Abstract/2017/09002/_OP_4B_02__KLOTHO_SUPPLEMENTATION_ATTENUATES_BLOOD.102.aspx
Klotho Gene Deficiency Causes Salt-Sensitive Hypertension via Monocyte Chemotactic Protein-1/CC Chemokine Receptor 2–Mediated Inflammation https://jasn.asnjournals.org/content/26/1/121
In Vivo klotho Gene Transfer Ameliorates Angiotensin II-Induced Renal Damage https://www.ahajournals.org/doi/full/10.1161/01.hyp.0000013734.33441.ea
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Electrically stimulated acupuncture increases renal blood flow through …
Aug 22, 2018 – Electrically stimulated acupuncture increases renal blood flow through exosome- carried miR-181. Klein JD(1), Wang XH(1). Author information: