The Taipei Veterans General Hospital (TVGH) and National Taiwan University Hospital (NTUH) yesterday said their collaborative research team made a breakthrough in identifying two key proteins — TRPM8 and DNAJB4 — that can slow the progression of chronic kidney disease.
More than 2 million people have chronic kidney disease in Taiwan, and the nation has one of the highest dialysis prevalence rates in the world, which influenced the research team to find methods to effectively minimize the deterioration of their condition and reduce the burden on the health system.
A research team led by TVGH Department of Medicine director Tarng Der-cherng (唐德成), NTUH Department of Medicine’s nephrology division chief Huang Jenq-wen (黃政文) and National Taiwan University’s Graduate Institute of Physiology professor Lee Tzong-shyuan (李宗玄) reported their breakthrough finding at TVGH.
Photo: CNA
The kidneys filter waste to make urine and maintain the body’s water and electrolyte balance.
Chronic kidney disease occurs when the kidneys are damaged for more than three months, resulting in incomplete recovery of their structure or function, Tarng said.
Lee said chronic kidney disease is closely associated with the development of Alzheimer’s disease and some cardiovascular diseases, adding that because previous studies found TRPM8 and DNAJB4 to be associated with the two types of disease, the team focused on finding the two proteins’ association with kidney disease.
The team found that the more severe the chronic kidney disease, the higher the protein expression of TRPM8 and DNAJB4, and by inhibiting the expression of these proteins, inflammation and fibrosis in the kidneys were effectively reduced, thereby slowing chronic kidney disease progression, he said.
TRPM8 is generally thought to be associated with membrane calcium channels, while some studies have shown that DNAJB4 plays an important role in stabilizing protein architecture in the body, the team said.
The team found that in the course of chronic kidney disease, an increase in TRPM8 expression leads to endothelial cell dysfunction, reduces nitric oxide production and damages the protective barrier of endothelial cells, aggravating renal fibrosis.
Meanwhile, DNAJB4 can attract more white blood cells, which worsens damage to the kidneys and causes apoptosis (cell death), they said.
The team said their research demonstrated the critical role of TRPM8 and DNAJB4 in chronic kidney disease progression and offers a new direction for clinical treatment, slowing the progression of kidney disease and improving people’s prognosis by inhibiting these proteins.
Lee said there are a few medications that were proven to inhibit TRPM8, so the team would continue to study the sequential relation of inhibiting the protein expressions and contribute to developing effective drugs for delaying the progression of kidney disease.
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