The Glomerulus According to the Mesangium

Abstract

The glomerulus is the functional unit for filtration of blood and formation of primary urine. This intricate structure is composed of the endothelium with its glycocalyx facing the blood, the glomerular basement membrane and the podocytes facing the urinary space of Bowman's capsule. The mesangial cells are the central hub connecting and supporting all these structures. The components as a unit ensure a high permselectivity hindering large plasma proteins from passing into the urine while readily filtering water and small solutes. There has been a long-standing interest and discussion regarding the functional contribution of the different cellular components but the mesangial cells have been somewhat overlooked in this context. The mesangium is situated in close proximity to all other cellular components of the glomerulus and should be considered important in pathophysiological events leading to glomerular disease. This review will highlight the role of the mesangium in both glomerular function and intra-glomerular crosstalk. It also aims to explain the role of the mesangium as a central component involved in disease onset and progression as well as signaling to maintain the functions of other glomerular cells to uphold permselectivity and glomerular health.

Heterogeneity of Platelet Derived Growth Factor Pathway Gene Expression Profile Defines Three Distinct Subgroups of Renal Cell Carcinomas

“…Normal kidney contains cells (in both parenchyma and stroma) with the ability to transdifferentiate in smooth muscle-like cells which might be recruited by ccRCC tumor vessels during their maturation. Mesangial cells (considered to be modified pericytes) (57) were recently classified by He et al (58) as having two distinct phenotypes: a pericyte-like phenotype and a fibroblast-like phenotype. Also, mesangial cells express FoxD1 gene which is also expressed by a population of progenitor cells that give rise to renal stroma, pericytes, vascular smooth muscle cells and mesangial cells (59)(60)(61).…”

Metabolic reprogramming: A novel therapeutic target in diabetic kidney disease

“…Glomerular mesangial cells (MCs) are specialized pericytes located around the glomerular capillaries within the renal corpuscle, and they synthesize the mesangial matrix and regulate glomerular hemodynamics via cell contraction and release various cytokines (Ebefors et al, 2021).Mesangial cell proliferation is stimulated in the early stage of DKD; subsequently, the growth of the cells is arrested, and they undergo hypertrophy and apoptosis (Khera et al, 2006;Tsai et al, 2020;Chen et al, 2022), contributing to glomerular sclerosis and a decline in the glomerular filtration rate. MCs exhibited higher basal respiration rates and reserved energy-production capacity, possibly making them more resistant to hyperglycemia.…”

The critical role of dysregulated autophagy in the progression of diabetic kidney disease

“…A series of inflammatory and oxidative stress responses generated by the massive protein leakage in DKD patients leads to morphological and functional dysfunction of the renal tubules, with epithelial mesenchymal transformation and cell detachment as well as apoptosis, ultimately leading to fibrosis ( Chen et al, 2020 ). In addition to this, pathological changes in DKD glomeruli are often accompanied by proliferation and expansion of the mesangial matrix, and activation of mesangial cells driven by factors such as hyperglycaemia and dyslipidaemia, accelerating glomerulosclerosis ( Ebefors et al, 2021 ).…”