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Kimberly Riley

Hometown:kim gooding
Greensboro, NC

Education:
Ph.D. in Cell and Developmental Biology from Vanderbilt University
B.S. in Biology with a minor in Chemistry from University of North Carolina, Chapel Hill

Kimberly Riley

Investigating the Role of CTGF in β Cell Proliferation


Studies have demonstrated the continued presence of insulin-expressing cells in pancreata from patients with long-standing Type 1 diabetes. Identifying factors that stimulate endogenous β-cell regeneration could facilitate β-cell mass expansion in these patients. CTGF affects proliferation, cell adhesion, extracellular matrix remodeling, and cell migration. CTGF is expressed in β-cells, ducts, and blood vessels during pancreas development, but is restricted to ducts and blood vessels in adult pancreata. Our lab discovered that CTGF is necessary for embryonic β-cell proliferation and islet morphogenesis. Animals lacking CTGF have increased glucagon+ cells and decreased β-cell proliferation.  In add

ition, CTGF over-expression in developing insulin-positive cells promotes proliferation of glucagon+ cells and immature insulin+ cells, without increasing endocrine differentiation.  CTGF did not enhance adult β-cell proliferation. Overall, CTGF works in both a paracrine and autocrine manner to promote embryonicβ-cell proliferation. We hypothesized that CTGF would promote adult β-cell regeneration after injury. We tested the ability of CTGF to promote β-cell proliferation using a model of of 50% β-cell destruction. Using a transgenic line that over-expresses the diphtheria toxin receptor under the control of the rat insulin promoter, β-cells are effectively and preferentially ablated upon injection of diphtheria toxin. After ablation, CTGF over-expression was induced for two or four weeks using the RIP-rtTA;TetO-CTGF (“Tet On”) transgene system.  Partial restoration of β-cell mass is observed at both time points, reaching 50% recovery of β-cell mass after four weeks of CTGF treatment. Recovery appears to be primarily via increased β-cell proliferation. No evidence for neogenesis has yet been observed. Thus, although adult β-cells are unresponsive to CTGF, it can induce replication in the setting of β-cell destruction. 

Publications:

Nonmuscle myosin II regulation of lung epithelial morphology.

Plosa EJ, Gooding KA, Zent R, Prince LS.

Dev Dyn. 2012 Nov;241(11):1770-81. doi: 10.1002/dvdy.23866. Epub 2012 Sep 25.

Riley, K. G. and M. Gannon (2015). Chapter 31 - Pancreas Development and Regeneration A2 - Moody, Sally A. Principles of Developmental Genetics (Second Edition). Oxford, Academic Press: 565-590. 

Henley KD, Gooding KA, Economides AN, Gannon M.
Am J Physiol Endocrinol Metab. 2012 Sep 15;303(6):E752-61. doi: 10.1152/ajpendo.00531.2011. Epub 2012   Jul 
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