APOL1 gene can induce kidney disease

According to an article published in the November 18 issue of the American Journal of Nephrology, the National Institutes of Health System for Children has discovered a gene, APOL1, which induces kidney disease. The new form of the mutated APOL1 gene increases the risk of chronic kidney disease among people of African descent. Using a powerful genetic approach and recombinant horse proteins, national researcher of children was able to mimic APOL1 in Drosophila renal cell pathology. It opens the door to identifying other proteins that interact with APOL1, which is an important first step in identifying kidney disease that is currently drug-free.

The advantages of Drosophila in biomedical research include its rapid generation time and unparalleled ability to explore the basic biological processes of human underlying diseases through rich, complex genetic tools. People of African descent usually inherit APOL1 mutant genes to protect Africans from sleeping sickness in Africa, but this gene increases the odds of developing certain types of kidney disease by 17 to 30 times or more. Individuals are at higher risk of being infected with human immunodeficiency Viruses (HIV). Drosophila kidney cells, called kidney cells, accurately mimic the pathological features of human kidney cells in APOL1-associated kidney disease.

"Kidney cells have striking structural and functional similarities to mammalian podocytes and proximal tubule cells," says Zhe Han, an advanced Drosophila expert and associate professor of cancer and immunology at the Center for Cancer and Immunology. "This provides us with a simple kidney disease model system."

In a recent study, Han's team cloned the mutated APOL1 gene in cells from podocytes cultured in patients with HIV-associated nephropathy. They created transgenic Drosophila, similar to human APOL1 kidney cells, and observed that the initial transgene caused an increase in cellular functional activity. However, as the flies age, APOL1 leads to decreased cell function, increased cell size, abnormal vesicular acidification and accelerated cell death.

"The main function of kidney cells is to filter proteins, remove toxins from flowing blood, reabsorb protein components and chelate harmful toxins. Surprisingly, these cells begin to become more active and play a temporary role at a higher level. The cells become bigger and stronger, but they can't sustain this enhancement," said Han. "Cells die and cell hypertrophy is the way the human heart responds to stress overload after swelling to twice its normal size. We think that kidney cells may use the same coping mechanism."

The Children's Research Group is a multidisciplinary team of members from the Cancer and Immunology Research Center, the Center for Genetic Medicine Research and the Department of Nephrology. The group also characterizes flies phenotypes associated with APOL1 gene expression, which will facilitate the design and implementation of Drosophila gene screening methods to identify proteins that interact with APOL1 and contribute to disease mechanisms. Such proteins represent potential therapeutic targeting targets. Transplantation is currently the only option for patients with kidney disease associated with APOL1.

"It's just the beginning," Han said. "Now that we have an ideal preclinical model, we plan to start testing out-of-the-box therapeutic compounds, such as different kinase inhibitors, to determine if they block any steps leading to kidney cell disease." Flarebio offers recombinant proteins such as recombinant Itgb2 at competitive prices.