Suppression of Mesangial Cell Proliferation and Extracellular Matrix Production in Streptozotocin-Induced Diabetic Mice by Adiponectin In Vitro and In Vivo

X. Huang; Y.-x. Su; H.-c. Deng; M.-x. Zhang; J. Long; Z.-g. Peng

doi:10.1055/s-0034-1375626

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2014; 46(10): 736-743
DOI: 10.1055/s-0034-1375626

Endocrine Research

Suppression of Mesangial Cell Proliferation and Extracellular Matrix Production in Streptozotocin-Induced Diabetic Mice by Adiponectin In Vitro and In Vivo

X. Huang^*

¹Department of Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China

,

Y.-x. Su^*

¹Department of Critical Care Medicine, The First Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China

,

H.-c. Deng

²Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China

,

M.-x. Zhang

³Department of Respiratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing, P. R. China

,

J. Long

²Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China

,

Z.-g. Peng

⁴Chongqing Key Laboratory of Ophthalmology, Chongqing, P. R. China

› Author Affiliations

Abstract

Renal growth, particularly hypertrophy, is a feature of diabetic nephropathy (DN). Adiponectin, an adipocyte-derived hormone, is an important regulator of cell proliferation. Recent studies have suggested that adiponectin has a protective effect in the kidney. The purpose of this study was to investigate the therapeutic effects and the underlying mechanisms of adiponectin in early DN. Mouse mesangial cells (MMCs) were cultured in media containing different concentrations of platelet-derived growth factor-BB (PDGF-BB) with or without adiponectin. MMC proliferation and expression of type IV collagen, laminin, and fibronectin were investigated. Streptozotocin-induced diabetic mice were injected intravenously with recombinant lentivirus encoding the mouse adiponectin gene (Lenti-Acdc-IRES-EGFP). Urinary microalbumin, serum adiponectin level, and expression of proliferating cell nuclear antigen, type IV collagen, laminin, and fibronectin were determined. Adiponectin inhibited the increases in MMC proliferation and expression of type IV collagen, laminin, and fibronectin induced by PDGF-BB. Adiponectin also effectively reduced renal cell proliferation and expression of type IV collagen, laminin, and fibronectin when it was introduced in vivo by lentivirus-mediated gene transfer. These findings suggest that adiponectin exerts renoprotective effects by inhibiting renal cell proliferation and reducing synthesis of extracellular matrix proteins, thus suppressing the development and progression of DN.

Key words

adiponectin - diabetic nephropathy - lentivirus - extracellular matrix proteins

Full Text

References

References
1 Steffes MW, Østerby R, Chavers B, Mauer SM. Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients. Diabetes 1989; 38: 1077-1081
2 Bangstad HJ, Rudberg S, Østerby R. Renal structural changes in patients with type 1 diabetes and microalbuminuria. In: The Kidney and Hypertension in Diabetes Mellitus by. Mogensen CE. (ed.) Dordrecht: Kluwer Academic Publishers; 2000: 211-225
3 Ayo SH, Radnik RA, Garoni JA, Glass WF. High glucose causes an increase in extracellular matrix proteins in cultured mesangial cells. Am J Pathol 1990; 136: 1339-1348
4 Yasuda T, Kondo S, Homma T, Harris RC. Regulation of extracellular matrix by mechanical stress in rat glomerular mesangial cells. J Clin Invest 1996; 98: 1991-2000
5 Mclennan SV, Fisher E, Martell SY, Death AK, Williams PF, Lyons JG, Yue DK. Effects of glucose on matrix metalloproteinase and plasmin activities in mesangial cells: possible role in diabetic nephropathy. Kidney Int 2000; 58 (Suppl) S81-S87
6 Abrass C. Diabetic nephropathy. Mechanisms of mesangial matrix expansion. West J Med 1995; 162: 318-321
7 Chestnut RE, Quarmby V. Evaluation of total IGF-I assay methods using samples from Type I and Type II diabetic patients. J Immunol Meth 2002; 259: 11-24
8 McLennan S, Wang X, Moreno V, Yue D, Twigg S. Connective tissue growth factor mediates high glucose effects on matrix degradation through tissue inhibitor of matrix metalloproteinase type 1: implications for diabetic nephropathy. Endocrinology 2004; 145: 5646-5655
9 Ziyadeh FN, Han DC. Involvement of transforming growth factor-beta and its receptors in the pathogenesis of diabetic nephrology. Kidney Int 1997; 60: S7-S11
10 Floege J, Ostendorf T, Janssen U, Burg M, Radeke HH, Vargeese C, Gill SC, Green S, Janjic N. Novel approach to specific growth factor inhibition in vivo: Antagonism of platelet-derived growth factor in glomerulonephritis by aptamers. Am J Pathol 1999; 154: 169-179
11 Pichler RH, Bassuk JA, Hugo C, Reed MJ, Eng E, Gordon KL, Johnson RJ. SPARC is expressed by mesangial cells in experimental mesangial proliferative nephritis and inhibits platelet-derived-growth-factor-medicated mesangial cell proliferation in vitro. Am J Pathol 1996; 148: 1153-1167
12 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiposeMost Abundant Gene Transcript 1). Biochem Biophys Res Commun 1996; 221: 286-289
13 Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995; 270: 26746-26749
14 Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MRS, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98: 2005-2010
15 Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423: 762-769
16 Cammisotto PG, Bendayan M. Adiponectin stimulates phosphorylation of AMP-activated protein kinase α in renal glomeruli. J Mol Histol 2008; 39: 579-584
17 Shimotomai T, Kakei M, Narita T, Koshimura J, Hosoba M, Kato M, Komatsuda A, Ito S. Enhanced urinary adiponectin excretion in IgA-nephropathy patients with proteinuria. Renal Failure 2005; 27: 323-328
18 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79-83
19 Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 2004; 24: 29-33
20 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930-1935
21 Navarro-González JF, Mora-Fernández C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 2008; 19: 433-442
22 Ohashi K, Iwatani H, Kihara S, Nakagawa Y, Komura N, Fujita K, Funahashi T. Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol 2007; 27: 1910-1917
23 Benaitreau D, Dieudonné MN, Santos ED, Leneveu MC, Mazancourt P, Pecquery R. Antiproliferative effects of adiponectin on human trophoblastic cell lines JEG-3 and BeWo. Mol Endocrinol 2009; 80: 1107-1114
24 Kim AY, Lee YS, Kim KH, Lee JH, Lee HK, Jang SH, Kim SE, Lee GY, Lee JW, Jung SA, Chung HY, Jeong S, Kim JB. Adiponectin represses colon cancer cell proliferation via AdipoR1-and-R2-mediated AMPK activation. Mol Endocrinol 2010; 24: 1441-1452
25 Park KK, Ahn JD, Lee IK, Magae J, Heintz NH, Kwak JY, Chang YC. Inhibitory effects of novel E2F decoy oligodeoxynucleotides on mesangial cell proliferation by coexpression of E2F/DP. Biochem Biophys Res Commun 2003; 308: 689-697
26 Battegay EJ, Raines EW, Seifert RA, Bowen-Pope DF, Ross R. TGF-β induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell 1990; 63: 515-524
27 Satoh H, Nguyen MA, Trujillo M, Imamura T, Usui I, Scherer PE, Olefsky JM. Adenovirus-mediated adiponectin expression augments skeletal muscle insulin sensitivity in male Wistar rats. Diabetes 2005; 54: 1304-1313
28 Sankaran D, Bankovic-Calic N, Peng CY, Ogborn MR, Aukema HM. Dietary flax oil during pregnancy and lactation retards disease progression in rat offspring with inherited kidney disease. Pediatr Res 2006; 60: 729-733
29 Gross ML, Ritz E, Schoof A, Helmke B, Parkman A, Tulp O, Münter K, Amann K. Renal damage in the SHR/N-cp type 2 diabetes model: comparison of an angiotensin-converting enzyme inhibitor and endothelin receptor blocker. Lab Invest 2003; 83: 1267-1277
30 Nyengaard J, Flyvbjerg A, Rasch R. The impact of renal growth, regression and regrowth in experimental diabetes mellitus on number and size of proximal and distal tubular cells in the rat kidney. Diabetologia 1993; 36: 1126-1131
31 Zeng XR, Jiang Y, Zhang SJ, Hao H, Lee M. DNA polymerase delta is involved in the cellular response to UV damage in human cells. J Biol Chem 1994; 269: 13748-13751
32 Chiarenza C, Filippini A, Tripiciano A, Beccari E, Palombi F. Platelet-derived growth factor-BB stimulates hypertrophy of peritubular smooth muscle cells from rat testis in primary cultures. Endocrinology 2000; 141: 2971-2981
33 Gross M, Ritz E, Schoof A, Adamczak M, Koch A, Tulp O, Amann K. Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes. Lab Invest 2004; 84: 452-464
34 Parameswaran N, Hall CS, Böck BC, Sparks HV, Gallo KA, Spielman WS. Mixed lineage kinase 3 inhibits phorbol myristoyl acetate-induced DNA synthesis but not osteopontin expression in rat mesangial cells. Mol Cell Biochem 2002; 241: 37-43
35 Floege J, Eitner F, Alpers CE. A new look at platelet-derived growth factor in renal disease. J Am Soc Nephrol 2008; 19: 12-23
36 Floege J, Topley N, Hoppe I, Barrett T, Resch K. Mitogenic effect of platelet-derived growth factor in human glomerular mesangial cells: modulation and/or suppression by inflammatory cytokines. Clin Exp Immunol 1991; 86: 334-341
37 Wallmon A, Fellström B, Larsson R, Floege J, Topley N, Ljunghall S. PDGF-BB but not PDGF-AA, stimulates calcium mobilization, activation of calcium channels and cell proliferation in cultured rat mesangial cells. Exp Nephrol 1993; 1: 238-244
38 Sterzel RB, Schulze-Lohoff E, Weber M, Goodman SL. Interactions between glomerular mesangial cells, cytokines, and extracellular matrix. J Am Soc Nephrol 1992; 2: S126-S131
39 Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. J Am Med Assoc 2004; 291: 1730-1737
40 Schulze MB, Shai I, Rimm EB, Li T, Rifai N, Hu FB. Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 2005; 54: 534-539
41 Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, Matsuzawa Y. Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB – binding protein and regulates growth factor – induced common postreceptor signal in vascular smooth muscle cell. Circulation 2002; 105: 2893-2898
42 Wang Y, Lam KS, Xu JY, Lu G, Xu LY, Cooper GJ, Xu A. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem 2005; 280: 18341-18347
43 Antoniades C, Antonopoulos A, Tousoulis D, Stefanadis C. Adiponectin: from obesity to cardiovascular disease. Obes Rev 2009; 10: 269-279
44 Saraheimo M, Forsblom C, Thorn L, Wadén J, Rosengård-Bärlund M, Heikkilä O, Groop PH. Serum adiponectin and progression of diabetic nephropathy in patients with type 1 diabetes. Diabetes Care 2008; 31: 1165-1169
45 Miner JH. Organogenesis of the kidney glomerulus: focus on the glomerular basement membrane. Organogenesis 2011; 7: 75-82
46 Eremina V, Baelde HJ, Quaggin SE. Role of the VEGF-A signaling pathway in the glomerulus: evidence for crosstalk between components of the glomerular filtration barrier. Nephron Physiol 2007; 106: 32-37
47 Sharma K, Ramachandra Rao S, Qiu G, Usui HK, Zhu Y, Dunn SR, Goldstein BJ. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 2008; 118: 1645-1656