Mechanisms of Scarring in Focal Segmental Glomerulosclerosis

Abstract

Focal segmental glomerulosclerosis (FSGS) presents with scar in parts of some glomeruli and often progresses to global and diffuse glomerulosclerosis. Podocyte injury is the initial target in primary FSGS, induced by a circulating factor. Several gene variants, for example, APOL1, are associated with increased susceptibility to FSGS. Primary FSGS may be due to genetic mutation in key podocyte genes. Increased work stress after loss of nephrons, epigenetic mechanisms, and various profibrotic pathways can contribute to progressive sclerosis, regardless of the initial injury. The progression of FSGS lesions also involves crosstalk between podocytes and other kidney cells, such as parietal epithelial cells, glomerular endothelial cells, and even tubular epithelial cells. New insights related to these mechanisms could potentially lead to new therapeutic strategies to prevent progression of FSGS.

Caveolin-1 in Kidney Chronic Antibody-Mediated Rejection: An Integrated Immunohistochemical and Transcriptomic Analysis Based on the Banff Human Organ Transplant (B-HOT) Gene Panel

“…We also provide evidence corroborating the value of nCounter ® Human Organ Transplant Panel Together with Cav-1, this latter pathway presented additional genes of potential clinical interest, such as CD44, TGFB1, ICAM-1, and VCAM-1. These four genes have been found to be related to focal and segmental glomerulosclerosis (FSGS), another relevant cause of long-term graft failure mediated by progressive fibrosis [37][38][39][40][41][42].…”

The Pathology Lesion Patterns of Podocytopathies: How and why?

“…The FSGS lesion is not due to a specific glomerular disease. Indeed, several conditions are well-described causative insults that lead to podocyte depletion such as hyperglycemia and insulin signaling, mechanical stress, angiotensin II, calcium signaling, viral infection, toxins, oxidants, and immunological injury ( Zhong et al, 2019 ). Thus, a wide range of disease states can lead to the development of the FSGS injury pattern, the common denominator being that the initiating events take place in podocytes.…”

Diverse Alterations of Glomerular Capillary Networks in Focal Segmental Glomerular Sclerosis

“…These include, podocyte injury to segmental sclerosis in FSGS, phenotypic changes in parietal epithelial cells; and crosstalk between glomerular epithelial and tubular epithelial cells and between glomerular endothelial or mesangial cells and podocytes. [12][13][14] Podocytes regulate proliferation and function of glomerular endothelial cells through vascular endothelial growth factor A (VEGFA) and endothelin-1 (EDN1) to maintain glomerular capillary loop homeostasis. There have been reports that conditional knockout of VEGFA in podocytes caused endothelial cell death and thrombotic microangiopathy (TMA).…”

“…Because FSGS is called “podocyte disease” or “podocytopathy” along with minimal-change nephrotic syndrome (NS), the initial target is podocyte injury. 1 , 12 , 13 Various constituent cells of the kidney have been reported to be involved in progression of the process. These include podocyte injury to segmental sclerosis in FSGS, phenotypic changes in parietal epithelial cells, and crosstalk between glomerular epithelial and tubular epithelial cells and between glomerular endothelial or mesangial cells and podocytes.…”

“…These include podocyte injury to segmental sclerosis in FSGS, phenotypic changes in parietal epithelial cells, and crosstalk between glomerular epithelial and tubular epithelial cells and between glomerular endothelial or mesangial cells and podocytes. 12 , 13 , 14 …”