Systems biology approach to transplant tolerance: proof of concept experiments using RNA interference (RNAi) to knock down hub genes in Jurkat and HeLa cells in vitro.

The Journal of Surgical Research
Wint Wah LwinAjai Khanna

Abstract

Systems biology is gaining importance in studying complex systems such as the functional interconnections of human genes [1]. To investigate the molecular interactions involved in T cell immune responses, we used databases of physical gene-gene interactions to constructed molecular interaction networks (interconnections) with R language algorithms. This helped to identify highly interconnected "hub" genes AT(1)P5C1, IL6ST, PRKCZ, MYC, FOS, JUN, and MAPK1. We hypothesized that suppression of these hub genes in the gene network would result in significant phenotypic effects on T cells and examined this in vitro. The molecular interaction networks were then analyzed and visualized with Cytoscape. Jurkat and HeLa cells were transfected with siRNA for the selected hub genes. Cell proliferation was measured using ATP luminescence and BrdU labeling, which were measured 36, 72, and 96 h after activation. Following T cell stimulation, we found a significant decrease in ATP production (P < 0.05) when the hub genes ATP5C1 and PRKCZ were knocked down using siRNA transfection, whereas no difference in ATP production was observed in siRNA transfected HeLa cells. However, HeLa cells showed a significant (P < 0.05) decrease in cell proliferati...Continue Reading

References

Jan 11, 2000·Nucleic Acids Research·G D BaderC W Hogue
Jul 2, 2002·Nature Medicine·Roger J Pomerantz
Sep 24, 2002·Nature Biotechnology·Haibin XiaBeverly L Davidson
Mar 15, 2003·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·G Mukherjee, S S Manna
May 24, 2005·Cell·Marc W Kirschner
May 10, 2006·PLoS Medicine·Andrew C AhnRussell S Phillips
Aug 15, 2006·Immunological Reviews·Maria Grazia RoncaroloMegan K Levings
Jun 30, 2007·Journal of Internal Medicine·B T Rouse
Oct 20, 2007·Nature Protocols·Melissa S ClineGary D Bader
Oct 31, 2007·Nature Clinical Practice. Rheumatology·Xavier Valencia, Peter E Lipsky
Feb 19, 2008·Pharmacology & Therapeutics·Vipul V JainPatricia W Finn
Mar 5, 2008·Clinical & Developmental Immunology·Nathalie CoolsZwi N Berneman
Mar 30, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·P F Halloran

❮ Previous
Next ❯

Citations

Apr 17, 2012·The Journal of Surgical Research·Reza F Saidi
Aug 8, 2014·Clinical and Experimental Medicine·Shivtia Trop-SteinbergReuven Or
Dec 15, 2020·Current Opinion in Organ Transplantation·Sunil M KurianChristopher L Marsh

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Related Papers

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
S A LodhiH U Meier-Kriesche
American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
M Martínez-LlordellaA Sánchez-Fueyo
American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Ying LiKoichi Tanaka
© 2022 Meta ULC. All rights reserved