Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism.

A common consequence of chronic renal disease is secondary hyperparathyroidism (SHPT) and is closely related to the mortality and morbidity of uremia patients. Secondary hyperparathyroidism (SHPT) is caused by excessive PTH production and release, as well as parathyroid enlargement. At present, the mechanism of cell proliferation in secondary hyperparathyroidism (SHPT) is not completely clear. Decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), and 1,25(OH)2D3 insufficiency all lead to a decrease in cell proliferation suppression, and activation of multiple pathways is also involved in cell proliferation in renal hyperparathyroidism. The interaction between the parathormone (PTH) and parathyroid hyperplasia and 1,25(OH)2D3 has received considerable attention. 1,25(OH)2D3 is commonly applied in the therapy of renal hyperparathyroidism. It regulates the production of parathormone (PTH) and parathyroid cell proliferation through transcription and post-transcription mechanisms. This article reviews the role of 1,25(OH)2D3 in parathyroid cells in secondary hyperparathyroidism and its current understanding and potential molecular mechanism.

Pro- and anti-fibrotic effects of vascular endothelial growth factor in chronic kidney diseases.

Renal fibrosis is the inevitable common end-point of all progressive chronic kidney diseases. The underlying mechanisms of renal fibrosis are complex, and currently there is no effective therapy against renal fibrosis. Renal microvascular rarefaction contributes to the progression of renal fibrosis; however, an imbalance between proangiogenic and antiangiogenic factors leads to the loss of renal microvasculature. Vascular endothelial growth factor (VEGF) is the most important pro-angiogenic factor. Recent studies have unraveled the involvement of VEGF in the regulation of renal microvascular rarefaction and fibrosis via various mechanisms; however, it is not clear whether it has anti-fibrotic or pro-fibrotic effect. This paper reviews the available evidence pertaining to the function of VEGF in the fibrotic process and explores the associated underlying mechanisms. Our synthesis will help identify the future research priorities for developing specialized treatments for alleviating or preventing renal fibrosis. Abbreviation: VEGF: vascular endothelial growth factor; CKD: chronic kidney disease; ESKD: end-stage kidney disease; ER: endoplasmic reticulum; VEGFR: vascular endothelial growth factor receptor; AKI: acute kidney injury; EMT: epithelial-to-mesenchymal transition; HIF: hypoxia-inducible factor; α-SMA: α smooth muscle actin; UUO: unilateral ureteral obstruction; TGF-ß: transforming growth factor-ß; PMT: pericyte-myofibroblast transition; NO: nitric oxide; NOS: nitric oxide synthase; nNOS: neuronal nitric oxide synthase; iNOS: inducible nitric oxide synthase; eNOS: endothelial nitric oxide synthase; sGC: soluble guanylate cyclase; PKG: soluble guanylate cyclase dependent protein kinases; UP R: unfolded protein response.

Magnesium in renal fibrosis.

PURPOSE: Renal fibrosis (RF) is the main pathological feature of chronic kidney disease (CKD). The main focus of research on treatment for CKD is to develop strategies that delay or prevent RF from progressing to end-stage renal disease (ESRD). Inflammation and oxidative stress occur during all stages of CKD. The magnesium cation (Mg2+) can reduce inflammation and oxidative stress, regulate apoptosis, and improve RF, and magnesium-based therapies are promising new treatments that can prevent RF. We reviewed the current evidence on the effects of magnesium in RF and examined the possible mechanism of magnesium in delaying RF. METHODS: We searched PubMed, Web of Science, and EMBASE for articles on magnesium and fibrosis, with a focus on magnesium and RF. RESULTS: Inflammation, oxidative stress, and apoptosis are related to the occurrence of CKD. Previous research showed that Mg2+ inhibits the differentiation of inflammatory cells, down-regulates the production of inflammatory cytokines, reduces inflammation, and reduces the production of reactive oxygen species (ROS) and oxidative stress. In addition, Mg2+ also regulates apoptosis and protects renal tubular function. Magnesium may also regulate TRPM6/7, promote the secretion of klotho protein and improve renal fibrosis. Therefore, Mg2+ can protect the kidney from damage and slow down the progression of RF through many molecular and cellular effects. Some of the anti-fibrotic effects of Mg2+ may be related to its antagonism of intracellular Ca2+. CONCLUSION: Magnesium may prevent the progression of renal fibrosis and delay CKD by reducing renal inflammation and oxidative stress, and by regulating fibrosis-related signaling pathways and cytokines.