Journal News

MCP: Tracing damage pathways
in diabetic kidney disease

John Arnst
April 1, 2017

Diabetic kidney disease is the most common cause of kidney failure and can occur as a complication of both Type I and Type II diabetes. In a paper published in the journal of Molecular & Cellular Proteomics, researchers at the University of Toronto and the Institut Hospital del Mar d’Investigacions Mèdiques in Spain report a link between the proteomic changes caused by high levels of male sex hormones and impaired energy metabolism in diabetic kidney disease.

 


Patients with diabetic kidney disease can have kidneys with scarred glomeruli.
WIKIMEDIA COMMONS

“It’s been reported in previous clinical studies that male sex hormones predispose (patients) to many kidney diseases and lead to a more rapid progression and increased severity of kidney disease,” says Sergi Clotet, the first author on the paper and a postdoctoral researcher in the laboratory of Ana Konvalinka at the University of Toronto. “Our findings proposed this novel link between male sex (hormones), energy metabolism and oxidative stress in the kidneys of diabetic animals, which are indicators of mitochondrial damage.”

Diabetic kidney disease causes the clustered kidney capillaries, known as glomeruli, to leak high levels of proteins, such as albumin, into urine. The leakage eventually leads to anemia, chemical imbalance in the bloodstream and overall decline in kidney function. The disease can be stemmed if caught early on but may be exacerbated in men by elevated androgens.

Clotet and colleagues used a variation of the SILAC technique for their study. In traditional SILAC, which stands for stable-isotope labeling of amino acids in cell culture, the amino acids in cells are labeled with nonradioactive isotopes and quantified by mass spectrometry.

The SILAC variant, known as “spike-in,” enabled the investigators to bypass difficulties involved with labeling the primary proximal tubular cells, which don’t grow well in SILAC media, by labeling only transformed proximal tubular cells. The labeled transformed cell lysates then were combined with the unlabeled and stimulated primary cell lysates.

The investigators stimulated primary cells with 100 nanomolar doses of a sex hormone, either estradiol or dihydrotestosterone, and subjected them to mass spectrometry to identify the changes in metabolic regulation caused by each hormone.

After performing subsequent bioinformatics analyses, the researchers noticed that energy metabolism was impaired in the cells exposed to dihydrotestosterone. They validated their results by examining the expression of key enzymes involved in metabolism in kidneys of male and female normal and diabetic animals. The researchers then performed an enrichment analysis of their own data and a publicly available gene-expression data set generated from kidneys of patients with diabetes. With the analysis, the researchers were able to group and visualize significant functional categories. They found that oxidative stress was elevated significantly in the testosterone-treated samples from their dataset as well as in the kidneys of diabetic patients.

The researchers then decided to analyze oxidative stress levels and the sex differences in their animal groups, finding that the stress levels were increased in males of both normal and diabetic animals. “It’s a result that suggests that male sex is associated with more severe kidney disease,” says Clotet.

Clotet and colleagues intend to collect kidney biopsies from diabetic and nondiabetic male and female donors to validate their findings further as well as to look for biomarkers that could indicate early onset of diabetic kidney disease. “That could be a noninvasive way to predict sex-specific progression of diabetic and nondiabetic kidney diseases,” says Clotet. “At the end of the day, we want to explore more personalized treatments for kidney disease.”

John Arnst

John Arnst was a science writer for ASBMB Today.

Related articles

From the journals: December 2019
John Arnst, Jonathan Griffin, Kian Kamgar-Parsi, Angela Hopp & Laurel Oldach
From the journals: September 2019
Jonathan Griffin, Kian Kamgar-Parsi & Tori Zirul
From the journals: June/July 2019
Courtney Chandler, Isha Dey & Jonathan Griffin
From the journals: May 2019
Gelareh (Abulwerdi) Vinueza, Jonathan Griffin & Kerri Beth Boggs

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

Finding a third form of fat
Journal News

Finding a third form of fat

Oct. 26, 2021

When brown fat was discovered in human adults, it came as a surprise. A classic JBC study found another surprise: White fat cells could be coaxed into a phenotype resembling brown fat.

My cat’s coat is mostly white with dark tabby patches. What’s going on?
Science Communication

My cat’s coat is mostly white with dark tabby patches. What’s going on?

Oct. 24, 2021

A researcher uses a tweetorial to figure out the underlying genetics for their cat’s coat.

Dalit scientists face barriers in India’s top science institutes
Diversity

Dalit scientists face barriers in India’s top science institutes

Oct. 23, 2021

Despite decades-old inclusion policies, Dalits are systematically underrepresented in science institutes in India. Why?

‘It goes both ways’
Interview

‘It goes both ways’

Oct. 21, 2021

This year’s theme of “location, location, location” refers to the scenic meeting spot and to a new way of looking at lipids.

From the journals: JLR
Journal News

From the journals: JLR

Oct. 19, 2021

Predicting drug-induced lysosomal fat buildup. Minimizing side effects of atherosclerosis treatment. Finding a key to sepsis diagnosis and treatment. Read about papers on these topics recently published in the Journal of Lipid Research.

A new way of looking at concussions
News

A new way of looking at concussions

Oct. 17, 2021

Emerging research suggests that even mild hits to the head may damage the tiny lymphatic vessels that clear toxic chemicals and cellular debris from the brain.