Nicotine, Smoking, Podocytes and Diabetic Nephropathy.

Nicotine, Smoking, Podocytes and Diabetic Nephropathy. Am J Physiol Renal Physiol. 2021 Jan 18;: Authors: Jaimes EA, Zhou MS, Siddiqui M, Rezonzew G, Tian R, Seshan SV, Muwonge AN, Wong NJ, Azeloglu EU, Fornoni A, Merscher S, Raij L Abstract Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. Besides glycemic and blood pressure control, environmental factors such as cigarette smoking (CS) adversely affect the progression of DN. The effects of CS on DN progression have been attributed to combustion generated molecules without consideration to the role of nicotine (NIC), responsible for the addictive properties of both CS and electronic cigarettes (EC). Podocytes (POD) are essential to preserve the structure and function of the glomerular filtration barrier and strong evidence indicates that early POD loss promotes DN progression. We performed studies in human POD and in a mouse model of diabetes that develops nephropathy resembling human DN. We determined that NIC binding to podocytes in concentrations achieved with CS and EC activated NADPH oxidase, which sets in motion a dysfunctional molecular network integrated by COX2, known to induce podocyte injury; downregulation of AMPK, important for maintaining cellular energy stores and antioxidation and upregulation of CD36 that increased lipid uptake and promoted apoptosis. In diabetic mice NIC increased proteinuria, a recognized marker of CKD progression, accompa...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research