Yan Chun Li, Ph.D.

Function of the Vitamin D Endocrine System

Research Summary

My laboratory has long-standing interests in the vitamin D endocrine system and in the mechanisms of metabolic and inflammatory diseases. Our research interests cover the following areas. 

Diabetic Complications: Diabetic nephropathy is the most common renal complication of diabetes mellitus and a leading cause of renal failure. Hyperglycemia is the main cause of diabetic renal injury. The major manifestation of the disease includes glomerular sclerosis and tubulointerstitial fibrosis. Research projects in this area include: Reno-protective mechanisms of vitamin D/vitamin D receptor (VDR) signaling; Epigenetic mechanisms of diabetic renal injury; Roles of microRNAs in tubulointerstitial fibrosis; and Roles of endothelin receptors in diabetic nephropathy.

Gastrointestinal Disease: Inflammatory bowel disease (IBD) is the major inflammatory disorder affecting the gastrointestinal tract. This problem is manifested by chronic colonic inflammation. Colon cancer is a leading cause of cancer death in humans. Main research topics in this area include: Intestinal epithelial VDR signaling in colonic inflammation and colitis pathogenesis; and Mechanisms of vitamin D inhibition of colon cancer.

Inflammation and Acute Lung Injury: Innate immune response is the first line of defense in pathogen infection. Severe bacterial infection can cause systemic inflammation (sepsis) and death. Acute lung injury is a major complication of systemic inflammation. Main research topics include: Roles of vitamin D and microRNAs in inflammatory response and immune tolerance; Vitamin D and acute lung injury; MicroRNAs in the regulation of acute lung injury.

Lipid Metabolism, Energy Homeostasis and Atherosclerosis: Adipocytes play a major role in energy homeostasis. Imbalance of energy intake and energy expenditure can lead to obesity, a major cause of metabolic syndrome. Atherosclerosis is an important vascular disease caused by chronic vascular inflammation usually triggered by hyperlipidemia. Research topics include: Macrophage VDR signaling in atherosclerosis; Cholesterol synthesis and vitamin D metabolism; and Adipocyte VDR signaling and energy metabolism.

Selected Papers

Xiang W, Kong J, Chen S, Cao L-P, Qiao G, Zheng W, Liu W, Li X, Gardner DG, Li YC. (2005) Cardiac Hypertrophy in Vitamin D Receptor Knockout Mice: Role of the systemic and cardiac renin-angiotensin systems. Am. J. Physiol.  Endocrinol. Metab., 288: E125-E132.

Kong J, Grando SA, Li YC. (2006) Regulation of interleukin-1 family cytokines interleukin-1a, interleukin-1 receptor antagonist and interleukin-18 by 1,25-dihydroxyvitamin D3 in primary keratinocytes.  Journal of Immunology 176:3780-3787.

Kong J, Li YC. (2006) Molecular Mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells. Am. J. Physiol.  Endocrinol. Metab. 290:E916-E924.

Sun J, Kong J, Duan Y, Szeto, FL, Liao A, Madara JL, Li YC. (2006) Increased NF-kB activity in fibroblasts lacking the vitamin D receptor.  Am. J. Physiol.  Endocrinol. Metab. 291:E315-E322.

Zhang Z, Yuan W, Sun L, Szeto FL, Wong KE, Li X, Kong J, Li YC (2007) 1,25-Dihydroxy-vitamin D3 targeting of NF-kB suppresses high glucose-induced MCP-1 expression in mesangial cells. Kidney Int. 72:193–201.

Yuan W, Pan W, Kong J, Zheng W, Szeto FL, Wong KE, Cohen R, Klopot A, Zhang Z, Li YC. (2007) 1,25-Dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J. Biol. Chem. 282(41): 29821-29830.

Zhang Z, Sun L, Wang Y, Ning G, Minto AW, Kong J, Quigg RJ, Li YC. (2008) Renoprotective role of the vitamin D receptor in diabetic nephropathy. Kidney Int. 73:163-171.

Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC (2008) Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am. J. Physiol. Gastrointest Liver Physiol. 294: G208-G216.

Wang Q, Li YC, Wang J, Kong J, Qi Y, Quigg RJ, Li X (2008) miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor suppressor Rb2/p130. Proc. Natl. Acad. Sci. USA. 105: 2889-1894.  [PMC2268555]

Kong J, Zhang Z, Li D, Wong KE, Zhang Y, Szeto FL, Musch MW, Li YC (2008) Loss of vitamin D receptor produces polyuria by increasing thirst. J. Am. Soc. Nephrol. 19: 2396–2405.

Kong J, Qiao G, Zhang Z, Liu SQ, Li YC (2008) Targeted vitamin D receptor expression in juxtaglomerular cells suppresses renin expression independent of parathyroid hormone and calcium. Kidney Int. 74:1577-1581.

Zhang Z, Zhang Y, Ning G, Deb DK, Kong J, Li YC. (2008) Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase. Proc. Natl. Acad. Sci. USA. 105:15896-15901. [PMC2562415]

Wong KE, Szeto FL, Zhang W, Ye H, Kong J, Zhang Z, Sun XJ, Li YC (2009) Involvement of the vitamin D receptor in energy metabolism: Regulation of uncoupling proteins. Am. J. Physiol.  Endocrinol. Metab. 296:E820-E828. [PMC2670625]

Deb DK, Chen Y, Zhang Z, Zhang Y, Szeto FL, Wong KE, Kong J, Li YC (2009) 1,25-Dihydroxy-vitamin D3 suppresses high glucose-induced angiotensinogen expression in kidney cells by blocking the NF-kB pathway. Am. J. Physiol. Renal Physiol. 296: F1212–F1218. [PMC2681355]

Deb DK, Sun T, Wong K. Zhang Z, Ning G, Zhang Y, Kong J, Shi H, Chang A, Li YC. (2010) Combined vitamin D analog and AT1 receptor antagonist synergistically block the development of kidney disease in a model of Type 2 diabetes. Kidney Int. 77:1000-1009.

Zhang Y, Kong J, Deb DK, Chang A, Li YC. (2010) Vitamin D receptor attenuates renal damage in obstructive nephropathy by blocking the renin-angiotensin system. J. Am. Soc. Nephrol.21:966-973. [PMC2900963]

Kong J, Kim E, Wei M, Sun T, Li G, Liu SQ, Li X, Zhao Q, Bhan I, Thadhani R, Li YC. (2010) Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats. Am. J. Pathol. 177:622-631. [PMC2913045]

Wong KE, Kong J, Zhang W, Szeto FL, Ye H, Deb DK, Brady MJ, Li YC. (2011) Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice. J. Biol. Chem. 286:33804-33810.

Deb DK, Wang Y, Zhang Z, Nie H, Huang X, Yuan Z, Chen Y, Zhao Q, Li YC. (2011) Molecular mechanism underlying 1,25-dihydroxyvitamin D regulation of nephrin gene expression. J. Biol. Chem. 286:32011-32017.

Zheng W, Wong KE, Zhang Z, Dougherty U, Mustafi R, Kong J, Deb DK, Zheng H, Bissonnette M, Li YC. (2012) Inactivation of the vitamin D receptor in APCmin/+ mice reveals a critical role for the vitamin D receptor in intestinal tumor growth. Int. J. Cancer 130:10-19. PMID: 21328347