Loss of Calponin 2 causes age‐progressive proteinuria in mice. Issue 18 (18th September 2022)

• Record Type: Journal Article
• Authors: Hsieh, Tzu‐Bou; Jin, Jian‐Ping
• Is Part Of: Physiological reports. Volume 10:Issue 18(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-18
• Subjects: calponin 2 -- cytoskeleton -- podocytes -- proteinuria; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.15370
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: Proteinuria is a major manifestation of kidney disease, reflecting injuries of glomerular podocytes. Actin cytoskeleton plays a pivotal role in stabilizing the foot processes of podocytes against the hydrostatic pressure of filtration. Calponin is an actin associated protein that regulates mechanical tension‐related cytoskeleton functions and its role in podocytes has not been established. Here we studied the kidney phenotypes of calponin isoform 2 knockout (KO) mice. Urine samples were examined to quantify the ratio of albumin and creatinine. Kidney tissue samples were collected for histology and ultrastructural studies. A mouse podocyte cell line (E11) was used to study the expression and cellular localization of calponin 2. In comparison with wild‐type (WT) controls, calponin 2 KO mice showed age‐progressive high proteinuria and degeneration of renal glomeruli. High levels of calponin 2 are expressed in E11 podocytes and colocalized with actin stress fibers, tropomyosin and myosin IIA. Electron microscopy showed that aging calponin 2 KO mice had effacement of the podocyte foot processes and increased thickness of the glomerular basement membrane as compared to that of WT control. The findings demonstrate that deletion of calponin 2 aggravates age‐progressive degeneration of the glomerular structure and function as filtration barrier. The critical role of calponin 2 in podocytes suggests a molecular target for understanding the pathogenesis of proteinuria and therapeutic development. Abstract : Calponin 2 KO mice develop age‐progressive proteinuria. The data show significantly higher urine albumin/creatinine ratio in 18‐24 months old calponin 2 KO than that in age‐matched WT mice. (a) compared to 3‐8 months old WT group; (b) compared to age‐matched WT and 3‐8 months old KO groups.