| First Author | Hsieh TB | Year | 2022 |
| Journal | Physiol Rep | Volume | 10 |
| Issue | 18 | Pages | e15370 |
| PubMed ID | 36117313 | Mgi Jnum | J:329304 |
| Mgi Id | MGI:7343175 | Doi | 10.14814/phy2.15370 |
| Citation | Hsieh TB, et al. (2022) Loss of Calponin 2 causes age-progressive proteinuria in mice. Physiol Rep 10(18):e15370 |
| abstractText | 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. |
