Role of Podocyte Injury in Glomerulosclerosis
Finding new therapeutic targets of glomerulosclerosis treatment is an ongoing quest. Due to a living environment of various stresses and pathological stimuli, podocytes are prone to injuries; moreover, as a cell without proliferative potential, loss of podocytes is vital in the pathogenesis of glomerulosclerosis. Thus, sufficient understanding of factors and underlying mechanisms of podocyte injury facilitates the advancement of treating and prevention of glomerulosclerosis. The clinical symptom of podocyte injury is proteinuria, sometimes with loss of kidney functions progressing to glomerulosclerosis. Injury-induced changes in podocyte physiology and function are actually not a simple passive process, but a complex interaction of proteins that comprise the anatomical structure of podocytes at molecular levels. This chapter lists several aspects of podocyte injuries along with potential mechanisms, including glucose and lipid metabolism disorder, hypertension, RAS activation, micro-inflammation, immune disorder, and other factors. These aspects are not technically separated items, but intertwined with each other in the pathogenesis of podocyte injuries.
KeywordsPodocyte injury Glomerular sclerosis
This study was supported by grants from the National Key Research and Development Program of China (2018YFC1314004).
- Ando K, Ohtsu H, Uchida S, Kaname S, Arakawa Y, Fujita T et al (2014) Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2:944–953PubMedCrossRefGoogle Scholar
- Bianchi S, Baronti A, Cominotto R, Bigazzi R (2016) Lipid metabolism abnormalities in Chronic Kidney Disease. G Ital Nefrol 33: S68 Google Scholar
- Gu L, Hagiwara S, Fan Q, Tanimoto M, Kobata M, Yamashita M et al (2006) Role of receptor for advanced glycation end-products and signalling events in advanced glycation end-product-induced monocyte chemoattractant protein-1 expression in differentiated mouse podocytes. Nephrol Dial Transplant 21:299–313PubMedCrossRefGoogle Scholar
- Kobayashi N, Ueno T, Ohashi K, Yamashita H, Takahashi Y, Sakamoto K et al (2015) Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated beta1-integrin endocytosis. Am J Physiol Renal Physiol 308:F614–F626PubMedPubMedCentralCrossRefGoogle Scholar
- Merscher S, Pedigo CE, Mendez AJ (2014) Metabolism, energetics, and lipid biology in the podocyte-cellular cholesterol-mediated glomerular injury. Front Endocrinol (Lausanne) 5:169Google Scholar