Zhen Wang1,2, Jussara M do Carmo3,4, Alexandre A da Silva3,4, Yiling Fu3,4, John E Hall3,4. 1. Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS, 39216, USA. zwang3@umc.edu. 2. Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, USA. zwang3@umc.edu. 3. Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS, 39216, USA. 4. Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, USA.
Abstract
PURPOSE OF REVIEW: To discuss the importance of synergistic interactions of diabetes mellitus (DM) and hypertension (HT) in causing chronic kidney disease and the potential molecular mechanisms involved. RECENT FINDINGS: DM and HT are the two most important risk factors for chronic kidney disease (CKD) and development of end-stage renal disease (ESRD). The combination of HT and DM may synergistically promote the progression of renal injury through mechanisms that have not been fully elucidated. Hyperglycemia and other metabolic changes in DM initiate endoplasmic reticulum (ER) stress and mitochondrial (MT) adaptation in different types of glomerular cells. These adaptations appear to make the cells more vulnerable to HT-induced mechanical stress. Excessive activation of mechanosensors, possibly via transient receptor potential cation channel subfamily C member 6 (TRPC6), may lead to impaired calcium (Ca2+) homeostasis and further exacerbate ER stress and MT dysfunction promoting cellular apoptosis and glomerular injury. The synergistic effects of HT and DM to promote kidney injury may be mediated by increased intraglomerular pressure. Chronic activation of mechanotransduction signaling may amplify metabolic effects of DM causing cellular injury through a vicious cycle of impaired Ca2+ homeostasis, mitochondrial dysfunction, and ER stress.
PURPOSE OF REVIEW: To discuss the importance of synergistic interactions of diabetes mellitus (DM) and hypertension (HT) in causing chronic kidney disease and the potential molecular mechanisms involved. RECENT FINDINGS:DM and HT are the two most important risk factors for chronic kidney disease (CKD) and development of end-stage renal disease (ESRD). The combination of HT and DM may synergistically promote the progression of renal injury through mechanisms that have not been fully elucidated. Hyperglycemia and other metabolic changes in DM initiate endoplasmic reticulum (ER) stress and mitochondrial (MT) adaptation in different types of glomerular cells. These adaptations appear to make the cells more vulnerable to HT-induced mechanical stress. Excessive activation of mechanosensors, possibly via transient receptor potential cation channel subfamily C member 6 (TRPC6), may lead to impaired calcium (Ca2+) homeostasis and further exacerbate ER stress and MT dysfunction promoting cellular apoptosis and glomerular injury. The synergistic effects of HT and DM to promote kidney injury may be mediated by increased intraglomerular pressure. Chronic activation of mechanotransduction signaling may amplify metabolic effects of DM causing cellular injury through a vicious cycle of impaired Ca2+ homeostasis, mitochondrial dysfunction, and ER stress.
Authors: Jonas Sieber; Maja Tamara Lindenmeyer; Kapil Kampe; Kirk Nicholas Campbell; Clemens David Cohen; Helmut Hopfer; Peter Mundel; Andreas Werner Jehle Journal: Am J Physiol Renal Physiol Date: 2010-07-28
Authors: Zhen Wang; Yiling Fu; Jussara M do Carmo; Alexandre A da Silva; Xuan Li; Alan Mouton; Ana Carolina M Omoto; Jaylan Sears; John E Hall Journal: Am J Physiol Renal Physiol Date: 2021-12-06
Authors: Kathy K Griendling; Livia L Camargo; Francisco J Rios; Rhéure Alves-Lopes; Augusto C Montezano; Rhian M Touyz Journal: Circ Res Date: 2021-04-01 Impact factor: 17.367