Loss of Calponin 2 causes age‐progressive proteinuria in mice
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...
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| Format: | Article |
| Language: | English |
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Wiley
2022-09-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.15370 |
| _version_ | 1818017041729191936 |
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| author | Tzu‐Bou Hsieh Jian‐Ping Jin |
| author_facet | Tzu‐Bou Hsieh Jian‐Ping Jin |
| author_sort | Tzu‐Bou Hsieh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:21:43Z |
| format | Article |
| id | doaj.art-798cdee576b74a929831e2b9755bcd9e |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-04-14T07:21:43Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-798cdee576b74a929831e2b9755bcd9e2022-12-22T02:06:08ZengWileyPhysiological Reports2051-817X2022-09-011018n/an/a10.14814/phy2.15370Loss of Calponin 2 causes age‐progressive proteinuria in miceTzu‐Bou Hsieh0Jian‐Ping Jin1Department of Obstetrics & Gynecology Wayne State University School of Medicine Detroit Michigan USADepartment of Obstetrics & Gynecology Wayne State University School of Medicine Detroit Michigan USAAbstract 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.https://doi.org/10.14814/phy2.15370calponin 2cytoskeletonpodocytesproteinuria |
| spellingShingle | Tzu‐Bou Hsieh Jian‐Ping Jin Loss of Calponin 2 causes age‐progressive proteinuria in mice Physiological Reports calponin 2 cytoskeleton podocytes proteinuria |
| title | Loss of Calponin 2 causes age‐progressive proteinuria in mice |
| title_full | Loss of Calponin 2 causes age‐progressive proteinuria in mice |
| title_fullStr | Loss of Calponin 2 causes age‐progressive proteinuria in mice |
| title_full_unstemmed | Loss of Calponin 2 causes age‐progressive proteinuria in mice |
| title_short | Loss of Calponin 2 causes age‐progressive proteinuria in mice |
| title_sort | loss of calponin 2 causes age progressive proteinuria in mice |
| topic | calponin 2 cytoskeleton podocytes proteinuria |
| url | https://doi.org/10.14814/phy2.15370 |
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