Source Of Abnormal Hyperplasia Of Parathyroid Eosinophils in Uremic Environment

The parathyroid gland is an important endocrine gland that regulates mineral metabolism, water and salt metabolism, and many other body functions. Under physiological conditions, more than 90% of it is composed of chief cells, and eosinophils (oxyphil cells) account for only 1%. Secondary hyperparathyroidism (SHPT) is one of the most common complications in patients with chronic kidney disease. It not only causes bone metabolism disorders but is also an independent risk factor that leads to cardiovascular disease, and multiple organ damage and affects patient prognosis. In recent years, It has become one of the most challenging hot issues in the field of kidney disease. The histopathological characteristics of patients with SHPT are clonal hyperplasia of parathyroid cells. In severe cases, multiple nodules or adenomas may form, and abnormal eosinophil hyperplasia may occur, resulting in ineffective drug treatment and the need for parathyroidectomy. In-depth exploration of the mechanism of parathyroid hyperplasia in patients with kidney disease will not only help establish new clinical prevention and control strategies for SHPT but may also provide new perspectives for the diagnosis and treatment of other human gland hyperplasia diseases.

Click to Cisanche for kidney disease

Recently, the internationally renowned academic journal Kidney International published online the latest research results "Single-cell RNA sequencing reveals transdifferentiation of parathyroid chief cells into oxyphil cells" by the team of Professor Chen Jing, Director of the Nephrology Department of Huashan Hospital Affiliated to Fudan University and Deputy Director of the National Clinical Research Center for Geriatric Diseases. in patients with uremic secondary hyperparathyroidism", Dr. Mao Jianping, a full-time assistant researcher at the National Clinical Research Center for Geriatric Diseases, is the first author of the paper. Kidney International is the official journal of the International Society of Nephrology, with the latest impact factor (IF) of 19.6, currently ranking first among all academic journals in the field of nephrology.

research proposal

In this study, the researchers collected three pathological types of parathyroid nodules (main cell nodules, eosinophilic nodules, and mixed nodules) surgically removed from patients with uremic SHPT for single Cell transcriptome sequencing (scRNA-seq), molecular biology research and transplanted nude mice.

Research result

1 Parathyroid chief cells can transdifferentiate into eosinophils, exhibiting abnormal mitochondrial enrichment

By performing scRNA-seq analysis on mixed parathyroid nodules, researchers successfully established the first transcriptome map of human parathyroid glands and found that in addition to two types of intrinsic cells, chief cells, and eosinophils, parathyroid tissue In addition, it also contains a small number of macrophages, fibroblasts, endothelial cells, and T&NK cells. In addition, through quasi-chronological analysis, the researchers discovered for the first time that chief cells can transdifferentiate into eosinophils, a process manifested by the gradual enrichment of mitochondria.

2 Abnormal mitochondrial enrichment in eosinophils may be related to the uremic milieu

Further comparing the mitochondrial characteristics of chief cells and eosinophils, the researchers found that the content, production, and fusion of mitochondria in eosinophils were significantly higher than those of chief cells, but the oxidative respiration function of a single mitochondria in eosinophils was lower than that of chief cells, suggesting that Although eosinophils are rich in mitochondria, they suffer from abnormal mitochondrial metabolism. Joint analysis of scRNA-seq and previously published RNA-seq revealed that multiple pathways are involved in the transdifferentiation of chief cells into eosinophils, and these pathways are closely related to the uremia environment and mitochondrial production, suggesting that uremia-related signaling pathways may Promote the abnormal enrichment of mitochondria in chief cells and then transform into eosinophils.

3 After leaving the uremic environment, the abnormal mitochondrial enrichment phenotype of eosinophils was significantly improved

Notably, when parathyroid chief cells or eosinophilic nodules from uremic patients were transplanted into nude mice to escape the uremic environment, the mitochondrial content and cellular proliferation of these two types of nodules were significantly reduced. Further transcriptome sequencing analysis found that the phenotype of eosinophilic nodules was significantly improved after transplantation into nude mice, as shown by a significant reduction in mitochondrial enrichment and eosinophilic proportion in the nodules.

Analysis conclusion

In summary, this study is the first to depict the human parathyroid single-cell transcriptome map and proves that parathyroid chief cells transdifferentiate into eosinophils in a uremic environment, and eosinophils are enriched with a large number of mitochondria and have abnormal mitochondrial metabolism. These findings not only give us a new understanding of the morphological changes of parathyroid glands but also strengthen the important role of mitochondrial function in the process of cell transdifferentiation and proliferation, providing a new perspective on the mechanism of multi-organ damage caused by kidney disease. It provides a new model of mitochondrial metabolic abnormality disease for life science research.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.