台灣的末期腎病的發生率與盛行率在世界44國中居第一。最近流病研究發現單是腹部肥胖就可引起微白蛋白尿與慢性腎病的組織病理特徵，其發生可能早於高血壓與高血糖。腹部肥胖、第二型糖尿病、脂質代謝異常與胰島素阻抗者，其血中含有高濃度游離脂肪酸，促使腎間質細胞堆積脂質，過度分泌基質蛋白如collagen及fibronectin等，與慢性腎病腎絲球纖維化有極大相關性。
本實驗以小鼠腎間質細胞 (Mouse mesangial cell; MC)為模式，以200 μM oleate誘發腎間質細胞堆積脂質、分泌促纖維化生長因子transforming growth factor-β(TGF-β)，與誘發細胞基質蛋白過度生成，並探討數種植物萃取物的影響。結果發現，茉莉、菊花、桂花甲醇萃物，丁香、迷迭香、紫蘇、花椒、鼠尾草、百里香、洋香菜、茴香乙醇萃物，以及苜蓿乙酸乙脂萃物可顯著抑制腎間質細胞TGF-β的分泌，而甘草乙醇萃物、山苦瓜乙酸乙酯萃物則無顯著影響。選擇可最有效抑制TGF-β分泌的桂花、菊花甲醇萃物做進一步研究，發現桂花甲醇萃物可降低細胞內三酸甘油酯及膽固醇含量，菊花甲醇萃物在高劑量時可降低細胞內三酸甘油酯及膽固醇含量，兩者均可顯著抑制腎間質細胞fibronectin mRNA表現並抑制fibronectin過度分泌。另外桂花甲醇萃物可抑制oleate所誘發之reactive oxygen species (ROS)生成，而菊花甲醇萃物可抑制oleate所誘發之extracellular signal-regulated kinase (ERK)磷酸化。
以上結果顯示桂花、菊花甲醇萃物可降低高游離脂肪酸所誘發腎間質促纖維化生長因子分泌、脂質堆積與基質蛋白増生，對於腹部肥胖所導致的腎絲球纖維化可能有預防效果。

Recent epidemiological studies show central obesity can induce microalbuminuria and pathological features of chronic kidney disease which may appear before hypertention and hyperglycemia. In obesity, type II diabetes, hyperlipidemia and conditions of insulin resistance, the concentration of circulating free fatty acid increases, and is associated with increasing lipid accumulation and extracellular matrix protein secretion (e.g collagen, fibronectin) in mesangial cells, which may result in glomerular fibrosis.
In this study, mouse mesangial cells (MCs) were treated with 200 μM oleate to increase the accumulation of lipids, the secretion of transforming growth factor (TGF)-β, and the expression of fibronectin. The protective effects of several herbal extracts were tested. We found the methanolic extracts of Jasmine, Chrysanthemu and Osmanthus, the ethanolic extracts of Clove, Perilla, Zanthoxylum, Salvia, Thymus, Parsle and Fennel, and the ethyl acetate extracts of Rosemary and Alfalfa significantly inhibited secretion of TGF-β induced by oleate in mouse MCs, but Glycyrrhiza ethanolic extract and bitter gourd ethyl acetate extract had no significant effects. Among them, Osmanthus fragrans (OF) and Chrysanthemum morifolium (CM) methanolic extracts, especially OF having the best TGF-β inhibition effects were investigated further. We observed that OF methanolic extract at concentration of 50-200 μg/mL decreased intracellular triacylglycerole and cholesterol levels, so did CM methanolic extract at high concentration (200 μg/mL) Both OF and CM methanolic extracts suppressed oleate-induced fibronectin mRNA overexpression, and fibronectin secretion in MCs. We also observed that OF methanolic extract decreased oleate-induced ROS production, and CM methanolic extract suppressed oleate-induced ERK phosphorylation.
In conclusion, OF and CM methanolic extracts prevent oleate-induced fibrosis factor, TGF-β, and ECM oversecretion, and decrease intracellular lipid accumulation. OF and CM methanolic extracts may have protective effects on high plasma free fatty acid-induced chronic kidney disease.

王姿晴 (2007). 促進或抑制巨噬細胞株分泌前列腺素E2的食材對於發炎反應的影響. 國立台灣大學微生物與生化學研究所 碩士論文
行政院衛生署國民健康局 (2006). 成人（20歲以上）代謝症候群之判定標準(2006台灣).
辛靜玫 (2010). 桂花、菊花與芝麻素對肝細胞脂質堆積、發炎與倉鼠脂肪肝之影響. 國立台灣師範大學人類發展與家庭學系 營養科學與教育組 碩士論文.
黃福龍 (2005). 台灣產桂花之安全性、抗致敏性氣喘及護肝功能之評估. 中華醫事學院 生物科技研究所 碩士論文.
Abboud, H. E. (1991). Resident glomerular cells in glomerular injury: mesangial cells. Semin Nephrol, 11(3), 304-311.
Abrass, C. K. (1995). Diabetic nephropathy. Mechanisms of mesangial matrix expansion. West J Med, 162(4), 318-321.
Abrass, C. K. (2004). Cellular lipid metabolism and the role of lipids in progressive renal disease. Am J Nephrol, 24(1), 46-53.
Abrass, C. K. (2006). Lipid metabolism and renal disease. Contrib Nephrol, 151, 106-121.
Abrass, C. K., Raugi, G. J., Gabourel, L. S., & Lovett, D. H. (1988). Insulin and insulin-like growth factor I binding to cultured rat glomerular mesangial cells. Endocrinology, 123(5), 2432-2439.
Abrass, C. K., Spicer, D., & Raugi, G. J. (1994). Insulin induces a change in extracellular matrix glycoproteins synthesized by rat mesangial cells in culture. Kidney Int, 46(3), 613-620.
Adelman, R. D., Restaino, I. G., Alon, U. S., & Blowey, D. L. (2001). Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. J Pediatr, 138(4), 481-485.
Agrawal, V., Shah, A., Rice, C., Franklin, B. A., & McCullough, P. A. (2009). Impact of treating the metabolic syndrome on chronic kidney disease. Nat Rev Nephrol, 5(9), 520-528.
Ahn, H. J., Park, J., Song, J. S., Ju, M. K., Kim, M. S., Ha, H., et al. (2007). Mycophenolic acid inhibits oleic acid-induced vascular smooth muscle cell activation by inhibiting cellular reactive oxygen species. Transplantation, 84(5), 634-638.
Azevedo, L. C., Pedro, M. A., Souza, L. C., de Souza, H. P., Janiszewski, M., da Luz, P. L., et al. (2000). Oxidative stress as a signaling mechanism of the vascular response to injury: the redox hypothesis of restenosis. Cardiovasc Res, 47(3), 436-445.
Bagby, S. P. (2004). Obesity-initiated metabolic syndrome and the kidney: a recipe for chronic kidney disease? J Am Soc Nephrol, 15(11), 2775-2791.
Benigni, A., Gagliardini, E., Tomasoni, S., Abbate, M., Ruggenenti, P., Kalluri, R., et al. (2004). Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy. Kidney Int, 65(6), 2193-2200.
Berfield, A. K., Chait, A., Oram, J. F., Zager, R. A., Johnson, A. C., & Abrass, C. K. (2006). IGF-1 induces rat glomerular mesangial cells to accumulate triglyceride. Am J Physiol Renal Physiol, 290(1), F138-147.
Bethesda, M. (2007). US Renal Data System,USRDS 2007. Annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States, national institutes of health, national institute of diabetes and digestive and kidney disease. US Renal Data System, Annual data report, 11.
Bodkin, N. L., Alexander, T. M., Ortmeyer, H. K., Johnson, E., & Hansen, B. C. (2003). Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction. J Gerontol A Biol Sci Med Sci, 58(3), 212-219.
Bokemeyer, D., Sorokin, A., & Dunn, M. J. (1996). Multiple intracellular MAP kinase signaling cascades. Kidney Int, 49(5), 1187-1198.
Border, W. A., & Noble, N. A. (1993). Cytokines in kidney disease: the role of transforming growth factor-beta. Am J Kidney Dis, 22(1), 105-113.
Bruneval, P., Bariety, J., Belair, M. F., Mandet, C., Heudes, D., & Nicoletti, A. (2002). Mesangial expansion associated with glomerular endothelial cell activation and macrophage recruitment is developing in hyperlipidaemic apoE null mice. Nephrol Dial Transplant, 17(12), 2099-2107.
Cha, D. R., Zhang, X., Zhang, Y., Wu, J., Su, D., Han, J. Y., et al. (2007). Peroxisome proliferator activated receptor alpha/gamma dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice. Diabetes, 56(8), 2036-2045.
Chagnac, A., Weinstein, T., Korzets, A., Ramadan, E., Hirsch, J., & Gafter, U. (2000). Glomerular hemodynamics in severe obesity. Am J Physiol Renal Physiol, 278(5), F817-822.
Chen, J., Muntner, P., Hamm, L. L., Jones, D. W., Batuman, V., Fonseca, V., et al. (2004). The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med, 140(3), 167-174.
Cheng, D. W., Jiang, Y., Shalev, A., Kowluru, R., Crook, E. D., & Singh, L. P. (2006). An analysis of high glucose and glucosamine-induced gene expression and oxidative stress in renal mesangial cells. Arch Physiol Biochem, 112(4-5), 189-218.
Cheng, J., Diaz Encarnacion, M. M., Warner, G. M., Gray, C. E., Nath, K. A., & Grande, J. P. (2005). TGF-beta1 stimulates monocyte chemoattractant protein-1 expression in mesangial cells through a phosphodiesterase isoenzyme 4-dependent process. Am J Physiol Cell Physiol, 289(4), C959-970.
Cooper, M. E. (1998). Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet, 352(9123), 213-219.
Coresh, J., Selvin, E., Stevens, L. A., Manzi, J., Kusek, J. W., Eggers, P., et al. (2007). Prevalence of chronic kidney disease in the United States. JAMA, 298(17), 2038-2047.
Cuspidi, C., Meani, S., Fusi, V., Severgnini, B., Valerio, C., Catini, E., et al. (2004). Metabolic syndrome and target organ damage in untreated essential hypertensives. J Hypertens, 22(10), 1991-1998.
Cusumano, A. M., Bodkin, N. L., Hansen, B. C., Iotti, R., Owens, J., Klotman, P. E., et al. (2002). Glomerular hypertrophy is associated with hyperinsulinemia and precedes overt diabetes in aging rhesus monkeys. Am J Kidney Dis, 40(5), 1075-1085.
DeFronzo, R. A., Cooke, C. R., Andres, R., Faloona, G. R., & Davis, P. J. (1975). The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest, 55(4), 845-855.
el Touny, S., Khan, W., & Hannun, Y. (1990). Regulation of platelet protein kinase C by oleic acid. Kinetic analysis of allosteric regulation and effects on autophosphorylation, phorbol ester binding, and susceptibility to inhibition. J Biol Chem, 265(27), 16437-16443.
Freedland, E. S. (2004). Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review. Nutr Metab (Lond), 1(1), 12.
Fukuda, N., Tahira, Y., Matsuda, H., & Matsumoto, K. (2009). Transforming growth factor-beta as a treatment target in renal diseases. J Nephrol, 22(6), 708-715.
Fumo, P., Kuncio, G. S., & Ziyadeh, F. N. (1994). PKC and high glucose stimulate collagen alpha 1 (IV) transcriptional activity in a reporter mesangial cell line. Am J Physiol, 267(4 Pt 2), F632-638.
Gavras, I., & Gavras, H. (2002). Angiotensin II as a cardiovascular risk factor. J Hum Hypertens, 16 Suppl 2, S2-6.
Genestra, M. (2007). Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal, 19(9), 1807-1819.
Ha, H., & Lee, H. B. (2003). Reactive oxygen species and matrix remodeling in diabetic kidney. J Am Soc Nephrol, 14(8 Suppl 3), S246-249.
Ha, H., Yu, M. R., Choi, Y. J., Kitamura, M., & Lee, H. B. (2002). Role of high glucose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells. J Am Soc Nephrol, 13(4), 894-902.
Hall, J. E., Henegar, J. R., Dwyer, T. M., Liu, J., Da Silva, A. A., Kuo, J. J., et al. (2004). Is obesity a major cause of chronic kidney disease? Adv Ren Replace Ther, 11(1), 41-54.
Haneda, M., Araki, S., Togawa, M., Sugimoto, T., Isono, M., & Kikkawa, R. (1997). Mitogen-activated protein kinase cascade is activated in glomeruli of diabetic rats and glomerular mesangial cells cultured under high glucose conditions. Diabetes, 46(5), 847-853.
Haneda, M., Koya, D., Isono, M., & Kikkawa, R. (2003). Overview of glucose signaling in mesangial cells in diabetic nephropathy. J Am Soc Nephrol, 14(5), 1374-1382.
Haraldsson, B., Nystrom, J., & Deen, W. M. (2008). Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev, 88(2), 451-487.
Hayashida, T., Poncelet, A. C., Hubchak, S. C., & Schnaper, H. W. (1999). TGF-beta1 activates MAP kinase in human mesangial cells: a possible role in collagen expression. Kidney Int, 56(5), 1710-1720.
Hayashida, T., & Schnaper, H. W. (2004). High ambient glucose enhances sensitivity to TGF-beta1 via extracellular signal--regulated kinase and protein kinase Cdelta activities in human mesangial cells. J Am Soc Nephrol, 15(8), 2032-2041.
Henegar, J. R., Bigler, S. A., Henegar, L. K., Tyagi, S. C., & Hall, J. E. (2001). Functional and structural changes in the kidney in the early stages of obesity. J Am Soc Nephrol, 12(6), 1211-1217.
Hirschberg, R., & Adler, S. (1998). Insulin-like growth factor system and the kidney: physiology, pathophysiology, and therapeutic implications. Am J Kidney Dis, 31(6), 901-919.
Hu, C. Q., Chen, K., Shi, Q., Kilkuskie, R. E., Cheng, Y. C., & Lee, K. H. (1994). Anti-AIDS agents, 10. Acacetin-7-O-beta-D-galactopyranoside, an anti-HIV principle from Chrysanthemum morifolium and a structure-activity correlation with some related flavonoids. J Nat Prod, 57(1), 42-51.
Huh, K. H., Ahn, H. J., Park, J., Ju, M. K., Song, J. S., Kim, M. S., et al. (2009). Mycophenolic acid inhibits oleic acid-induced mesangial cell activation through both cellular reactive oxygen species and inosine monophosphate dehydrogenase 2 pathways. Pediatr Nephrol, 24(4), 737-745.
Huot, J., Lambert, H., Lavoie, J. N., Guimond, A., Houle, F., & Landry, J. (1995). Characterization of 45-kDa/54-kDa HSP27 kinase, a stress-sensitive kinase which may activate the phosphorylation-dependent protective function of mammalian 27-kDa heat-shock protein HSP27. Eur J Biochem, 227(1-2), 416-427.
Ihm, C. G., Park, J. K., Hong, S. P., Lee, T. W., Cho, B. S., Kim, M. J., et al. (1998). A high glucose concentration stimulates the expression of monocyte chemotactic peptide 1 in human mesangial cells. Nephron, 79(1), 33-37.
Irani, K. (2000). Oxidant signaling in vascular cell growth, death, and survival : a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res, 87(3), 179-183.
Ishii, H., Jirousek, M. R., Koya, D., Takagi, C., Xia, P., Clermont, A., et al. (1996). Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science, 272(5262), 728-731.
Isono, M., Cruz, M. C., Chen, S., Hong, S. W., & Ziyadeh, F. N. (2000). Extracellular signal-regulated kinase mediates stimulation of TGF-beta1 and matrix by high glucose in mesangial cells. J Am Soc Nephrol, 11(12), 2222-2230.
Jiang, Y., Cheng, D. W., Levi, E., & Singh, L. P. (2006). IGF-1 increases laminin, cyclin D1, and p21Cip1 expression in glomerular mesangial cells: an investigation of the intracellular signaling pathway and cell-cycle progression. J Cell Biochem, 98(1), 208-220.
K/DOQI (2002). K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis, 39(2 Suppl 1), S1-266.
Kanamori, H., Matsubara, T., Mima, A., Sumi, E., Nagai, K., Takahashi, T., et al. (2007). Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. Biochem Biophys Res Commun, 360(4), 772-777.
Kliewer, S. A., Sundseth, S. S., Jones, S. A., Brown, P. J., Wisely, G. B., Koble, C. S., et al. (1997). Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A, 94(9), 4318-4323.
Koya, D., Haneda, M., Nakagawa, H., Isshiki, K., Sato, H., Maeda, S., et al. (2000). Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC beta inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes. FASEB J, 14(3), 439-447.
Kreisberg, J. I. (1982). Insulin requirement for contraction of cultured rat glomerular mesangial cells in response to angiotensin II: possible role for insulin in modulating glomerular hemodynamics. Proc Natl Acad Sci U S A, 79(13), 4190-4192.
Kreisberg, J. I., Venkatachalam, M., & Troyer, D. (1985). Contractile properties of cultured glomerular mesangial cells. Am J Physiol, 249(4 Pt 2), F457-463.
Kriz, W., Elger, M., Lemley, K., & Sakai, T. (1990). Structure of the glomerular mesangium: a biomechanical interpretation. Kidney Int Suppl, 30, S2-9.
Kurella, M., Lo, J. C., & Chertow, G. M. (2005). Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol, 16(7), 2134-2140.
Lee do, Y., Choi, G., Yoon, T., Cheon, M. S., Choo, B. K., & Kim, H. K. (2009). Anti-inflammatory activity of Chrysanthemum indicum extract in acute and chronic cutaneous inflammation. J Ethnopharmacol, 123(1), 149-154.
Lee, H. (2000). Oxidized LDL, glomerular mesangial cells and collagen. Diabetes Res Clin Pract, 45, 6.
Lee, H. H., Lin, C. T., & Yang, L. L. (2007). Neuroprotection and free radical scavenging effects of Osmanthus fragrans. J Biomed Sci, 14(6), 819-827.
Li, J., Lee, Y. S., Choi, J. S., Sung, H. Y., Kim, J. K., Lim, S. S., et al. (2010). Roasted licorice extracts dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking Akt activation and TGF-beta signaling. Phytomedicine, 17(10), 800-810.
Lin, S., Sahai, A., Chugh, S. S., Pan, X., Wallner, E. I., Danesh, F. R., et al. (2002). High glucose stimulates synthesis of fibronectin via a novel protein kinase C, Rap1b, and B-Raf signaling pathway. J Biol Chem, 277(44), 41725-41735.
Lupia, E., Elliot, S. J., Lenz, O., Zheng, F., Hattori, M., Striker, G. E., et al. (1999). IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: implications for diabetic nephropathy. Diabetes, 48(8), 1638-1644.
Massy, Z. A., Kim, Y., Guijarro, C., Kasiske, B. L., Keane, W. F., & O'Donnell, M. P. (2000). Low-density lipoprotein-induced expression of interleukin-6, a marker of human mesangial cell inflammation: effects of oxidation and modulation by lovastatin. Biochem Biophys Res Commun, 267(2), 536-540.
Mene, P., Caenazzo, C., Pugliese, F., Cinotti, G. A., D'Angelo, A., Garbisa, S., et al. (2001). Monocyte/mesangial cell interactions in high-glucose co-cultures. Nephrol Dial Transplant, 16(5), 913-922.
Mene, P., Simonson, M. S., & Dunn, M. J. (1989). Physiology of the mesangial cell. Physiol Rev, 69(4), 1347-1424.
Mishra, R., & Simonson, M. S. (2008). Oleate induces a myofibroblast-like phenotype in mesangial cells. Arterioscler Thromb Vasc Biol, 28(3), 541-547.
Morales, E., Valero, M. A., Leon, M., Hernandez, E., & Praga, M. (2003). Beneficial effects of weight loss in overweight patients with chronic proteinuric nephropathies. Am J Kidney Dis, 41(2), 319-327.
Mule, G., Nardi, E., Cottone, S., Cusimano, P., Volpe, V., Piazza, G., et al. (2005). Influence of metabolic syndrome on hypertension-related target organ damage. J Intern Med, 257(6), 503-513.
Mulyadi, L., Stevens, C., Munro, S., Lingard, J., & Bermingham, M. (2001). Body fat distribution and total body fat as risk factors for microalbuminuria in the obese. Ann Nutr Metab, 45(2), 67-71.
Nishida, Y., Oda, H., & Yorioka, N. (1999). Effect of lipoproteins on mesangial cell proliferation. Kidney Int Suppl, 71, S51-53.
Nishizuka, Y. (1992). Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science, 258(5082), 607-614.
Olivetti, G., Anversa, P., Rigamonti, W., Vitali-Mazza, L., & Loud, A. V. (1977). Morphometry of the renal corpuscle during normal postnatal growth and compensatory hypertrophy. A light microscope study. J Cell Biol, 75(2 Pt 1), 573-585.
Overall, C. M., Wrana, J. L., & Sodek, J. (1989). Independent regulation of collagenase, 72-kDa progelatinase, and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor-beta. J Biol Chem, 264(3), 1860-1869.
Palaniappan, L., Carnethon, M., & Fortmann, S. P. (2003). Association between microalbuminuria and the metabolic syndrome: NHANES III. Am J Hypertens, 16(11 Pt 1), 952-958.
Peralta, C. A., Kurella, M., Lo, J. C., & Chertow, G. M. (2006). The metabolic syndrome and chronic kidney disease. Curr Opin Nephrol Hypertens, 15(4), 361-365.
Pete, G., Hu, Y., Walsh, M., Sowers, J., & Dunbar, J. C. (1996). Insulin-like growth factor-I decreases mean blood pressure and selectively increases regional blood flow in normal rats. Proc Soc Exp Biol Med, 213(2), 187-192.
Rhee, S. G. (2006). Cell signaling. H2O2, a necessary evil for cell signaling. Science, 312(5782), 1882-1883.
Rowe, J. W., Young, J. B., Minaker, K. L., Stevens, A. L., Pallotta, J., & Landsberg, L. (1981). Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes, 30(3), 219-225.
Ruan, X. Z., Varghese, Z., & Moorhead, J. F. (2009). An update on the lipid nephrotoxicity hypothesis. Nat Rev Nephrol, 5(12), 713-721.
Ruan, X. Z., Varghese, Z., Powis, S. H., & Moorhead, J. F. (1999). Human mesangial cells express inducible macrophage scavenger receptor. Kidney Int, 56(2), 440-451.
Sarafidis, P. A., & Ruilope, L. M. (2006). Insulin resistance, hyperinsulinemia, and renal injury: mechanisms and implications. Am J Nephrol, 26(3), 232-244.
Schaffer, J. E. (2003). Lipotoxicity: when tissues overeat. Curr Opin Lipidol, 14(3), 281-287.
Schlondorff, D. (1987). The glomerular mesangial cell: an expanding role for a specialized pericyte. FASEB J, 1(4), 272-281.
Schmitz-Peiffer, C. (2002). Protein kinase C and lipid-induced insulin resistance in skeletal muscle. Ann N Y Acad Sci, 967, 146-157.
Sharma, K., Jin, Y., Guo, J., & Ziyadeh, F. N. (1996). Neutralization of TGF-beta by anti-TGF-beta antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice. Diabetes, 45(4), 522-530.
Sharma, K., & Ziyadeh, F. N. (1994). The emerging role of transforming growth factor-beta in kidney diseases. Am J Physiol, 266(6 Pt 2), F829-842.
Shulman, G. I. (2000). Cellular mechanisms of insulin resistance. J Clin Invest, 106(2), 171-176.
Strang, W. r. (2006). Vander’s human physiology. The mechanisms of body function.
Sun, L., Halaihel, N., Zhang, W., Rogers, T., & Levi, M. (2002). Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus. J Biol Chem, 277(21), 18919-18927.
Tortora, G. J. (2005). Principles of Human Anatomy.
Unger, R. H. (2003a). Lipid overload and overflow: metabolic trauma and the metabolic syndrome. Trends Endocrinol Metab, 14(9), 398-403.
Unger, R. H. (2003b). Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology, 144(12), 5159-5165.
Unger, R. H., & Orci, L. (2002). Lipoapoptosis: its mechanism and its diseases. Biochim Biophys Acta, 1585(2-3), 202-212.
Varga, J., & Jimenez, S. A. (1986). Stimulation of normal human fibroblast collagen production and processing by transforming growth factor-beta. Biochem Biophys Res Commun, 138(2), 974-980.
Walker, W. G. (1993). Relation of lipid abnormalities to progression of renal damage in essential hypertension, insulin-dependent and non insulin-dependent diabetes mellitus. Miner Electrolyte Metab, 19(3), 137-143.
Wang, H. S., Gan, D. H., Zhang, X. P., & Pan, Y. M. (2010). Antioxidant capacity of the extracts from pulp of Osmanthus fragrans and its components. LWT-Food Science and Technology, 43, 7.
Wang, L., Kwak, J. H., Kim, S. I., He, Y., & Choi, M. E. (2004). Transforming growth factor-beta1 stimulates vascular endothelial growth factor 164 via mitogen-activated protein kinase kinase 3-p38alpha and p38delta mitogen-activated protein kinase-dependent pathway in murine mesangial cells. J Biol Chem, 279(32), 33213-33219.
Wang, Y., & Oram, J. F. (2005). Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a phospholipase D2 pathway. J Biol Chem, 280(43), 35896-35903.
Weigert, C., Sauer, U., Brodbeck, K., Pfeiffer, A., Haring, H. U., & Schleicher, E. D. (2000). AP-1 proteins mediate hyperglycemia-induced activation of the human TGF-beta1 promoter in mesangial cells. J Am Soc Nephrol, 11(11), 2007-2016.
Wen, C. P., Cheng, T. Y., Tsai, M. K., Chang, Y. C., Chan, H. T., Tsai, S. P., et al. (2008). All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan. Lancet, 371(9631), 2173-2182.
Wilmer, W. A., Dixon, C. L., & Hebert, C. (2001). Chronic exposure of human mesangial cells to high glucose environments activates the p38 MAPK pathway. Kidney Int, 60(3), 858-871.
Wu, D., Peng, F., Zhang, B., Ingram, A. J., Kelly, D. J., Gilbert, R. E., et al. (2009). PKC-beta1 mediates glucose-induced Akt activation and TGF-beta1 upregulation in mesangial cells. J Am Soc Nephrol, 20(3), 554-566.
Wu, L. C., Chang, L. H., Chen, S. H., Fan, N. C., & Ho, J. A. (2009). Antioxidant activity and melanogenesis inhibitory effect of the acetonic extract of Osmanthus fragrans: A potential natural and functional food flavor additive. LWT-Food Science and Technology, 42, 7.
Ziyadeh, F. N. (2004). Mediators of diabetic renal disease: the case for tgf-Beta as the major mediator. J Am Soc Nephrol, 15 Suppl 1, S55-57.