AMP-dependent kinase stimulates the expression of αKlotho.
CKD
FGF23
longevity
metformin
phenformin
Journal
FEBS open bio
ISSN: 2211-5463
Titre abrégé: FEBS Open Bio
Pays: England
ID NLM: 101580716
Informations de publication
Date de publication:
01 Aug 2024
01 Aug 2024
Historique:
revised:
14
06
2024
received:
31
07
2023
accepted:
17
07
2024
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
2
8
2024
Statut:
aheadofprint
Résumé
Renal αKlotho along with fibroblast growth factor 23 regulates phosphate and vitamin D metabolism. Its cleavage yields soluble Klotho controlling intracellular processes. αKlotho has anti-inflammatory and antioxidant effects and is nephro- and cardioprotective. AMP-dependent kinase (AMPK) is a nephro- and cardioprotective energy sensor. Given that both αKlotho and AMPK have beneficial effects in similar organs, we studied whether AMPK regulates αKlotho gene expression in Madin-Darby canine kidney, normal rat kidney 52E, and human kidney 2 cells. Using quantitative real-time PCR and western blotting, we measured αKlotho expression upon pharmacological manipulation or siRNA-mediated knockdown of AMPKα. AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) enhanced αKlotho expression, an effect reduced in the presence of AMPK inhibitor compound C or siRNA targeting AMPK catalytic α-subunits (α1 and α2). Similarly, AMPK activators metformin and phenformin upregulated αKlotho transcripts. Taken together, our results suggest that AMPK is a powerful inducer of αKlotho and could thereby contribute to the development of future therapeutic interventions.
Identifiants
pubmed: 39090792
doi: 10.1002/2211-5463.13872
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : Fo 695/6-1
Informations de copyright
© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Kuro‐o M (2012) Klotho in health and disease. Curr Opin Nephrol Hypertens 21, 362–368.
Yoshiko Y, Wang H, Minamizaki T, Ijuin C, Yamamoto R, Suemune S, Kozai K, Tanne K, Aubin JE and Maeda N (2007) Mineralized tissue cells are a principal source of FGF23. Bone 40, 1565–1573.
Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW et al. (2006) Regulation of fibroblast growth factor‐23 signaling by klotho. J Biol Chem 281, 6120–6123.
Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S and Yamashita T (2006) Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444, 770–774.
Toan NK, Tai NC, Kim S‐A and Ahn S‐G (2020) Soluble klotho regulates bone differentiation by upregulating expression of the transcription factor EGR‐1. FEBS Lett 594, 290–300.
Leifheit‐Nestler M, Wagner MA, Richter B, Piepert C, Eitner F, Böckmann I, Vogt I, Grund A, Hille SS, Foinquinos A et al. (2021) Cardiac fibroblast growth factor 23 excess does not induce left ventricular hypertrophy in healthy mice. Front Cell Dev Biol 9, 745892.
Chu C, Elitok S, Zeng S, Xiong Y, Hocher CF, Hasan AA, Krämer BK and Hocher B (2021) C‐terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival. BMC Nephrol 22, 125.
di Giuseppe R, Kühn T, Hirche F, Buijsse B, Dierkes J, Fritsche A, Kaaks R, Boeing H, Stangl GI and Weikert C (2015) Plasma fibroblast growth factor 23 and risk of cardiovascular disease: results from the EPIC‐Germany case‐cohort study. Eur J Epidemiol 30, 131–141.
Bär L, Stournaras C, Lang F and Föller M (2019) Regulation of fibroblast growth factor 23 (FGF23) in health and disease. FEBS Lett 593, 1879–1900.
Lang F, Leibrock C, Pandyra AA, Stournaras C, Wagner CA and Föller M (2018) Phosphate homeostasis, inflammation and the regulation of FGF‐23. Kidney Blood Press Res 43, 1742–1748.
Takashi Y and Fukumoto S (2020) Phosphate‐sensing and regulatory mechanism of FGF23 production. J Endocrinol Investig 43, 877–883.
Razzaque MS (2009) The FGF23‐klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol 5, 611–619.
Voelkl J, Alesutan I, Leibrock CB, Quintanilla‐Martinez L, Kuhn V, Feger M, Mia S, Ahmed MS, Rosenblatt KP, Kuro‐O M et al. (2013) Spironolactone ameliorates PIT1‐dependent vascular osteoinduction in klotho‐hypomorphic mice. J Clin Invest 123, 812–822.
Razzaque MS, Sitara D, Taguchi T, St‐Arnaud R and Lanske B (2006) Premature aging‐like phenotype in fibroblast growth factor 23 null mice is a vitamin D‐mediated process. FASEB J 20, 720–722.
Kuro‐o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E et al. (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390, 45–51.
Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H et al. (2005) Suppression of aging in mice by the Hormone Klotho. Science 309, 1829–1833.
Miao J, Huang J, Luo C, Ye H, Ling X, Wu Q, Shen W and Zhou L (2021) Klotho retards renal fibrosis through targeting mitochondrial dysfunction and cellular senescence in renal tubular cells. Physiol Rep 9, e14696.
Xie J, Cha S‐K, An S‐W, Kuro‐o M, Birnbaumer L and Huang C‐L (2012) Cardioprotection by klotho through downregulation of TRPC6 channels in the mouse heart. Nat Commun 3, 1238.
Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, Shiizaki K, Gotschall R, Schiavi S, Yorioka N et al. (2011) Klotho inhibits transforming growth factor‐beta1 (TGF‐beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem 286, 8655–8665.
Wolf I, Levanon‐Cohen S, Bose S, Ligumsky H, Sredni B, Kanety H, Kuro‐o M, Karlan B, Kaufman B, Koeffler HP et al. (2008) Klotho: a tumor suppressor and a modulator of the IGF‐1 and FGF pathways in human breast cancer. Oncogene 27, 7094–7105.
Zhou L, Li Y, Zhou D, Tan RJ and Liu Y (2013) Loss of klotho contributes to kidney injury by derepression of Wnt/β‐catenin signaling. J Am Soc Nephrol 24, 771–785.
Kuro‐o M (2008) Klotho as a regulator of oxidative stress and senescence. Biol Chem 389, 233–241.
Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, Miyoshi M, Ogawa Y, Castrillon DH, Rosenblatt KP et al. (2005) Regulation of oxidative stress by the anti‐aging hormone klotho. J Biol Chem 280, 38029–38034.
Hui H, Zhai Y, Ao L, Cleveland JC, Liu H, Fullerton DA and Meng X (2017) Klotho suppresses the inflammatory responses and ameliorates cardiac dysfunction in aging endotoxemic mice. Oncotarget 8, 15663–15676.
Stapleton D et al. (1996) Mammalian AMP‐activated protein kinase subfamily. J Biol Chem 271, 611–614.
Kim J, Yang G, Kim Y, Kim J and Ha J (2016) AMPK activators: mechanisms of action and physiological activities. Exp Mol Med 48, e224.
Lin S‐C and Hardie DG (2018) AMPK: sensing glucose as well as cellular energy status. Cell Metab 27, 299–313.
Qi D and Young LH (2015) AMPK: energy sensor and survival mechanism in the ischemic heart. Trends Endocrinol Metab 26, 422–429.
Ruderman NB, Carling D, Prentki M and Cacicedo JM (2013) AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest 123, 2764–2772.
Jeon S‐M (2016) Regulation and function of AMPK in physiology and diseases. Exp Mol Med 48, e245.
Saurav S and Manna SK (2022) Profilin upregulation induces autophagy through stabilization of AMP‐activated protein kinase. FEBS Lett 596, 1765–1777.
Mohammed I, Hollenberg MD, Ding H and Triggle CR (2021) A critical review of the evidence that metformin is a putative anti‐aging drug that enhances Healthspan and extends lifespan. Front Endocrinol 12, 718942.
Agius L, Ford BE and Chachra SS (2020) The metformin mechanism on gluconeogenesis and AMPK activation: the metabolite perspective. Int J Mol Sci 21, 3240.
Sanchez‐Rangel E and Inzucchi SE (2017) Metformin: clinical use in type 2 diabetes. Diabetologia 60, 1586–1593.
Maltese G, Psefteli P‐M, Rizzo B, Srivastava S, Gnudi L, Mann GE and Siow RCM (2017) The anti‐ageing hormone klotho induces Nrf2‐mediated antioxidant defences in human aortic smooth muscle cells. J Cell Mol Med 21, 621–627.
Hu M‐C, Kuro‐o M and Moe OW (2010) Klotho and kidney disease. J Nephrol 23(Suppl 16), S136–S144.
Shi M, Flores B, Gillings N, Bian A, Cho HJ, Yan S, Liu Y, Levine B, Moe OW and Hu MC (2016) αKlotho mitigates progression of AKI to CKD through activation of autophagy. J Am Soc Nephrol 27, 2331–2345.
Hu MC, Shi M, Gillings N, Flores B, Takahashi M, Kuro‐o M and Moe OW (2017) Recombinant α‐klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy. Kidney Int 91, 1104–1114.
Liu F, Wu S, Ren H and Gu J (2011) Klotho suppresses RIG‐I‐mediated senescence‐associated inflammation. Nat Cell Biol 13, 254–262.
Sugiura H, Yoshida T, Shiohira S, Kohei J, Mitobe M, Kurosu H, Kuro‐o M, Nitta K and Tsuchiya K (2012) Reduced klotho expression level in kidney aggravates renal interstitial fibrosis. Am J Physiol Renal Physiol 302, F1252–F1264.
Hu MC, Shi M, Zhang J, Quiñones H, Griffith C, Kuro‐o M and Moe OW (2011) Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 22, 124–136.
Chung C‐P et al. (2017) α‐Klotho expression determines nitric oxide synthesis in response to FGF‐23 in human aortic endothelial cells. PLoS One 12, e0176817.
Kusaba T, Okigaki M, Matui A, Murakami M, Ishikawa K, Kimura T, Sonomura K, Adachi Y, Shibuya M, Shirayama T et al. (2010) Klotho is associated with VEGF receptor‐2 and the transient receptor potential canonical‐1 Ca2+ channel to maintain endothelial integrity. Proc Natl Acad Sci USA 107, 19308–19313.
Xie J, Yoon J, An S‐W, Kuro‐o M and Huang C‐L (2015) Soluble klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate. J Am Soc Nephrol 26, 1150–1160.
Zhou X, Li SY, Wang Z, Yu L and Jiang H (2015) Klotho protein: a potential therapeutic agent during myocardial ischemia and reperfusion. Int J Cardiol 191, 227–228.
Donate‐Correa J, Martín‐Núñez E, Mora‐Fernández C, Muros‐de‐Fuentes M, Pérez‐Delgado N and Navarro‐González JF (2015) Klotho in cardiovascular disease: current and future perspectives. World J Biol Chem 6, 351–357.
Abraham CR, Mullen PC, Tucker‐Zhou T, Chen CD and Zeldich E (2016) Klotho is a neuroprotective and cognition‐enhancing protein. Vitam Horm 101, 215–238.
Ewendt F, Feger M and Föller M (2020) Role of fibroblast growth factor 23 (FGF23) and αKlotho in cancer. Front Cell Dev Biol 8, 601006.
Buhl ES, Jessen N, Pold R, Ledet T, Flyvbjerg A, Pedersen SB, Pedersen O, Schmitz O and Lund S (2002) Long‐term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome. Diabetes 51, 2199–2206.
Declèves A‐E, Sharma K and Satriano J (2014) Beneficial effects of AMP‐activated protein kinase agonists in kidney ischemia‐reperfusion: autophagy and cellular stress markers. Nephron Exp Nephrol doi: 10.1159/000368932
Cieslik KA, Taffet GE, Crawford JR, Trial J, Mejia Osuna P and Entman ML (2013) AICAR‐dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction. J Mol Cell Cardiol 63, 26–36.
Li X, Liu J, Lu Q, Ren D, Sun X, Rousselle T, Tan Y and Li J (2019) AMPK: a therapeutic target of heart failure‐not only metabolism regulation. Biosci Rep 39, BSR20181767.
Rajani R, Pastor‐Soler NM and Hallows KR (2017) Role of AMP‐activated protein kinase in kidney tubular transport, metabolism, and disease. Curr Opin Nephrol Hypertens 26, 375–383.
Nesti L and Natali A (2017) Metformin effects on the heart and the cardiovascular system: a review of experimental and clinical data. Nutr Metab Cardiovasc Dis 27, 657–669.
Han Y, Xie H, Liu Y, Gao P, Yang X and Shen Z (2019) Effect of metformin on all‐cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta‐analysis. Cardiovasc Diabetol 18, 96.
Luo F, Das A, Chen J, Wu P, Li X and Fang Z (2019) Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management. Cardiovasc Diabetol 18, 54.
Song A, Zhang C and Meng X (2021) Mechanism and application of metformin in kidney diseases: An update. Biomed Pharmacotherapy 138, 111454.
Miller RA and Birnbaum MJ (2010) An energetic tale of AMPK‐independent effects of metformin. J Clin Invest 120, 2267–2270.
Luo L, Guo J, Li Y, Liu T and Lai L (2023) Klotho promotes AMPK activity and maintains renal vascular integrity by regulating the YAP signaling pathway. Int J Med Sci 20, 194–205.
Lee J, Tsogbadrakh B, Yang S, Ryu H, Kang E, Kang M, Kang HG, Ahn C and Oh KH (2021) Klotho ameliorates diabetic nephropathy via LKB1‐AMPK‐PGC1α‐mediated renal mitochondrial protection. Biochem Biophys Res Commun 534, 1040–1046.
Zhou S, Hum J, Taskintuna K, Olaya S, Steinman J, Ma J and Golestaneh N (2023) The anti‐aging hormone klotho promotes retinal pigment epithelium cell viability and metabolism by activating the AMPK/PGC‐1α pathway. Antioxidants 12, 385.