Dr Soon Wei Wong1,2, Dr DARLING ROJAS-CANALES1,2, Ms ELISE TUCKER2, Dr JONATHAN GLEADLE1,2
1Department of Renal Medicine, Flinders Medical Centre, Bedford Park, Australia, 2College of Medicine and Public Health, Flinders University, Bedford Park, Australia
Aim:
To examine the role of IGF signalling on the hypertrophic response mechanism in renal tubular cells.
Background:
The IGF pathway is a key regulator of compensatory growth. Acting both systemically (i.e. growth hormone-IGF1 axis), and also locally, promoting cell proliferation and/or hyper¬trophy via the mTOR pathway. The mTOR pathway integrates many biochemical reactions, including translation, transcription, and lipid synthesis. It is also a key mediator of compensatory renal hypertrophy post nephrectomy. More recently, mTOR-mediated lipogenesis has been shown to be critical in fuelling cell proliferation and organ growth. However, the direct effect of IGF signalling on lipogenesis and renal cell size has not been defined.
Method:
HK2 cells were serum starved for 48 hours and then treated with vehicle control (HCl) or IGF-1 (200ng/mL) in serum-free conditions for 48h. Then cell size, protein/DNA ratio, neutral lipid content (BODIPY) were determined by flow cytometry. Immunoblot for mature SREBP2 was used to determine the activation of lipogenesis.
Results:
HK2 cells treated with IGF-1 showed significantly increased in cell size by 9.5% (p<0.0001, n=18), protein/DNA ratio by 16% (p<0.05, n=3), neutral lipid content by 43% (p<0.001, n=10) and mature SREBP-2 protein (n=1). All statistical analysis was carried out with Student’s t-test.
Conclusion:
IGF-1 promotes the enlargement of proximal tubule cells by hypertrophy. These cells concurrently increase their lipid content which is likely driven by the activation of SREBP-2. Suggestive that IGF1 may directly activate cholesterol biosynthesis pathways during renal cell growth, which warrants further investigation.
Biography:
I am currently undertaking a post-doctoral position at Flinders Medical Centre. My research focuses on the mechanism underlying healthy compensatory kidney growth. When a healthy individual donates a kidney, their remaining kidney increase in size and excretory function by over 30%. The mechanism responsible for compensatory renal hypertrophy remains elusive. Therefore, my research aims to identify how the early growth signal is generated, how it is targeted to the kidney and what are the metabolic alterations required to generate hypertrophy.