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International Urology and Nephrology

, Volume 49, Issue 11, pp 2079–2086 | Cite as

High glucose stimulates cell proliferation and Collagen IV production in rat mesangial cells through inhibiting AMPK-KATP signaling

  • Bei Zhang
  • Yong-quan ShiEmail author
  • Jun-jie Zou
  • Xiang-fang Chen
  • Wei Tang
  • Fei Ye
  • Zhi-min Liu
Nephrology – Original Paper

Abstract

Purpose

The present study investigated the putative mechanisms underlying effects of KATP channel on high glucose (HG)-induced mesangial cell proliferation and tissue inhibitors of metalloproteinases (TIMP)-2 and Collagen IV production.

Methods

Rat mesangial cells were subjected to whole cell patch clamp to record the KATP channel currents under high glucose (HG, 30 mM) condition. Cell proliferation was measured using a CCK-8 assay. The production of TIMP-2 and Collagen IV and AMP-activated protein kinase (AMPK)-signaling pathway activity was assessed by ELISA and Western blotting, respectively. AMPK agonist (AICAR) was used to analyze the role of this kinase. The expression of KATP subunit (Kir6.1, Kir6.2, SUR1, SUR2A and SUR2B) was examined using quantitative real-time PCR (RT-PCR).

Results

We found that HG was significant decreases in the expression of Kir6.1, SUB2A and SUB2B, three subunits of KATP, TIMP-2 production, KATP channel activity and AMPK activity, while it promoted the cell proliferation and Collagen IV production in rat mesangial cells. Pretreatment with KATP selective opener (diazoxide, DZX) significantly inhibited HG-induced mesangial cell proliferation, Collagen IV production and decrease in KATP channel activity in rat mesangial cells, which were reversed by pretreatment of 5-hydroxydecanoate, a selective inhibitor of KATP. Moreover, AICAR pretreatment inhibited HG-induced decrease in KATP channel activity.

Conclusions

Taken together, activating AMPK-KATP signaling may protect against HG-induced mesangial cell proliferation and Collagen IV production, and, thereby, provides new insights into the molecular mechanisms underlying early diabetic nephropathy (DN).

Keywords

KATP channel AMP-activated protein kinase High glucose Cell proliferation Collagen IV 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Marques C, Mega C, Goncalves A, Rodrigues-Santos P, Teixeira-Lemos E (2014) Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals. Mediat Inflamm 2014:538737CrossRefGoogle Scholar
  2. 2.
    Panduru NM, Saraheimo M, Forsblom C, Thorn LM, Gordin D, Wadén J, Tolonen N, Bierhaus A, Humpert PM, Groop PH (2015) Urinary adiponectin is an independent predictor of progression to end-stage renal disease in patients with type 1 diabetes and diabetic nephropathy. Diabetes Care 38:883–890CrossRefPubMedGoogle Scholar
  3. 3.
    Burrows NR, Li Y, Geiss LS (2010) Incidence of treatment for end-stage renal disease among individuals with diabetes in the U.S. continues to decline. Diabetes Care 33:73–77CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Zoccali C, Kramer A, Jager K (2009) The databases: renal replacement therapy since 1989—the European Renal Association and European Dialysis and Transplant Association (ERA-EDTA). Clin J Am Soc Nephrol 4(Suppl 1):S18–S22CrossRefPubMedGoogle Scholar
  5. 5.
    Liu W, Liu P, Tao S, Deng Y, Li X, Lan T, Zhang X, Guo F, Huang W, Chen F, Huang H, Zhou SF (2008) Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose. Arch Biochem Biophys 475:128–134CrossRefPubMedGoogle Scholar
  6. 6.
    Catania JM, Chen G, Parrish AR (2007) Role of matrix metalloproteinases in renal pathophysiologies. Am J Physiol Renal Physiol 292:F905–F911CrossRefPubMedGoogle Scholar
  7. 7.
    Tency I, Verstraelen H, Kroes I, Holtappels G, Verhasselt B, Vaneechoutte M, Verhelst R, Temmerman M (2012) Imbalances between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in maternal serum during preterm labor. PLoS ONE 7:e49042CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Tanaka K, Essick EE, Doros G, Tanriverdi K, Connors LH, Seldin DC, Sam F (2013) Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases in cardiac amyloidosis. J Am Heart Assoc 2:e005868CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kolset SO, Reinholt FP, Jenssen T (2012) Diabetic nephropathy and extracellular matrix. J Histochem Cytochem 60:976–986CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Nichols CG (2006) KATP channels as molecular sensors of cellular metabolism. Nature 440:470–476CrossRefPubMedGoogle Scholar
  11. 11.
    Liu X, Duan P, Hu X, Li R, Zhu Q (2016) Altered KATP channel subunits expression and vascular reactivity in spontaneously hypertensive rats with age. J Cardiovasc Pharmacol 68:143–149CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Beall C, Watterson KR, McCrimmon RJ, Ashford ML (2013) AMPK modulates glucose-sensing in insulin-secreting cells by altered phosphotransfer to KATP channels. J Bioenerg Biomembr 45:229–241CrossRefPubMedGoogle Scholar
  13. 13.
    Distrutti E, Cipriani S, Renga B, Mencarelli A, Migliorati M, Cianetti S, Fiorucci S (2010) Hydrogen sulphide induces micro opioid receptor-dependent analgesia in a rodent model of visceral pain. Mol Pain 6:36CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Mori K, Yamashita Y, Teramoto N (2016) Effects of ZD0947, a novel and potent ATP-sensitive K+ channel opener, on smooth muscle-type ATP-sensitive K+ channels. Eur J Pharmacol 791:773–779CrossRefPubMedGoogle Scholar
  15. 15.
    Teramoto N (2006) Physiological roles of ATP-sensitive K+ channels in smooth muscle. J Physiol 572:617–624CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wheeler A, Wang C, Yang K, Fang K, Davis K, Styer AM, Mirshahi U, Moreau C, Revilloud J, Vivaudou M, Liu S, Mirshahi T, Chan KW (2008) Coassembly of different sulfonylurea receptor subtypes extends the phenotypic diversity of ATP-sensitive potassium (KATP) channels. Mol Pharmacol 74:1333–1344CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hardie DG, Ross FA, Hawley SA (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13:251–262CrossRefPubMedGoogle Scholar
  18. 18.
    Tsuboi T, da Silva Xavier G, Leclerc I, Rutter GA (2003) 5′-AMP-activated protein kinase controls insulin-containing secretory vesicle dynamics. J Biol Chem 278:52042–52051CrossRefPubMedGoogle Scholar
  19. 19.
    da Silva Xavier G, Leclerc I, Varadi A, Tsuboi T, Moule SK, Rutter GA (2003) Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression. Biochem J 371:761–774CrossRefGoogle Scholar
  20. 20.
    Kim MY, Lim JH, Youn HH, Hong YA, Yang KS, Park HS, Chung S, Ko SH, Shin SJ, Choi BS, Kim HW, Kim YS, Lee JH, Chang YS, Park CW (2013) Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1alpha axis in db/db mice. Diabetologia 56:204–217CrossRefPubMedGoogle Scholar
  21. 21.
    Lindegaard B, Matthews VB, Brandt C, Hojman P, Allen TL, Estevez E, Watt MJ, Bruce CR, Mortensen OH, Syberg S, Rudnicka C, Abildgaard J, Pilegaard H, Hidalgo J, Ditlevsen S, Alsted TJ, Madsen AN, Pedersen BK, Febbraio MA (2013) Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice. Diabetes 62:3064–3074CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Beall C, Hamilton DL, Gallagher J, Logie L, Wright K, Soutar MP, Dadak S, Ashford FB, Haythorne E, Du Q, Jovanović A, McCrimmon RJ, Ashford ML (2012) Mouse hypothalamic GT1-7 cells demonstrate AMPK-dependent intrinsic glucose-sensing behaviour. Diabetologia 55:2432–2444CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Chen PC, Kryukova YN, Shyng SL (2013) Leptin regulates KATP channel trafficking in pancreatic beta-cells by a signaling mechanism involving AMP-activated protein kinase (AMPK) and cAMP-dependent protein kinase (PKA). J Biol Chem 288:34098–34109CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhang B, Shi Y, Zou J, Chen X, Tang W, Ye F, Liu Z (2017) KATP channels in high glucose-induced rat mesangial cell proliferation and release of MMP-2 and fibronectin. Exp Ther Med 14:135–140CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Medeiros-Domingo A, Tan BH, Crotti L, Tester DJ, Eckhardt L, Cuoretti A, Kroboth SL, Song C, Zhou Q, Kopp D, Schwartz PJ, Makielski JC, Ackerman MJ (2010) Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes. Heart Rhythm 7:1466–1471CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    McTaggart JS, Clark RH, Ashcroft FM (2010) The role of the KATP channel in glucose homeostasis in health and disease: more than meets the islet. J Physiol 588:3201–3209CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Masia R, Enkvetchakul D, Nichols CG (2005) Differential nucleotide regulation of KATP channels by SUR1 and SUR2A. J Mol Cell Cardiol 39:491–501CrossRefPubMedGoogle Scholar
  28. 28.
    Yang SN, Wenna ND, Yu J, Yang G, Qiu H, Yu L, Juntti-Berggren L, Köhler M, Berggren PO (2007) Glucose recruits K(ATP) channels via non-insulin-containing dense-core granules. Cell Metab 6:217–228CrossRefPubMedGoogle Scholar
  29. 29.
    Hu K, Huang CS, Jan YN, Jan LY (2003) ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C. Neuron 38:417–432CrossRefPubMedGoogle Scholar
  30. 30.
    Gromada J, Franklin I, Wollheim CB (2007) Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev 28:84–116CrossRefPubMedGoogle Scholar
  31. 31.
    Liang W, Chen J, Mo L, Ke X, Zhang W, Zheng D, Pan W, Wu S, Feng J, Song M, Liao X (2016) ATP-sensitive K(+) channels contribute to the protective effects of exogenous hydrogen sulfide against high glucose-induced injury in H9c2 cardiac cells. Int J Mol Med 37:763–772CrossRefPubMedGoogle Scholar
  32. 32.
    Ashcroft FM (2005) ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest 115:2047–2058CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Banach M, Drozdz J, Okonski P, Rysz J (2005) Immunological aspects of the statins’ function in patients with heart failure: a report from the annual conference of ESC—heart failure 2005. Cell Mol Immunol 2:433–437PubMedGoogle Scholar
  34. 34.
    Hanley PJ, Mickel M, Loffler M, Brandt U, Daut J (2002) K(ATP) channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart. J Physiol 542:735–741CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lim A, Park SH, Sohn JW, Jeon JH, Park JH, Park JH, Song DK, Lee SH, Ho WK (2009) Glucose deprivation regulates KATP channel trafficking via AMP-activated protein kinase in pancreatic beta-cells. Diabetes 58:2813–2819CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tarasov AI, Girard CA, Ashcroft FM (2006) ATP sensitivity of the ATP-sensitive K+ channel in intact and permeabilized pancreatic beta-cells. Diabetes 55:2446–2454CrossRefPubMedGoogle Scholar
  37. 37.
    Han YE, Lim A, Park SH, Chang S, Lee SH, Ho WK (2015) Rac-mediated actin remodeling and myosin II are involved in KATP channel trafficking in pancreatic beta-cells. Exp Mol Med 47:e190CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Bei Zhang
    • 1
  • Yong-quan Shi
    • 1
    Email author
  • Jun-jie Zou
    • 1
  • Xiang-fang Chen
    • 1
  • Wei Tang
    • 1
  • Fei Ye
    • 1
  • Zhi-min Liu
    • 1
  1. 1.Department of EndocrinologyShanghai Changzheng HospitalShanghaiPeople’s Republic of China

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