Protective role of endorepellin in renal developmental programming
Adverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major co...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.929556/full |
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| author | Xiaoshan Tang Xiaoshan Tang Manqing Sun Manqing Sun Qian Shen Qian Shen Jia Rao Jia Rao Xue Yang Xue Yang Ye Fang Ye Fang Tianchao Xiang Tianchao Xiang Shanshan Xue Shanshan Xue Lei Sun Hong Xu Hong Xu |
| author_facet | Xiaoshan Tang Xiaoshan Tang Manqing Sun Manqing Sun Qian Shen Qian Shen Jia Rao Jia Rao Xue Yang Xue Yang Ye Fang Ye Fang Tianchao Xiang Tianchao Xiang Shanshan Xue Shanshan Xue Lei Sun Hong Xu Hong Xu |
| author_sort | Xiaoshan Tang |
| collection | DOAJ |
| description | Adverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major contributor to renal developmental programming. The differentially expressed protein perlecan, which we previously identified using proteomics, is an important extracellular matrix glycoprotein, and its domain V (endorepellin) can inhibit apoptosis through a paracrine form. In explanted mice embryonic metanephros, we found that endorepellin can rescue glomeruli-deficit phenotype resulting from malnutrition, and this protective effect was also verified in vivo using a renal developmental programming model which was given a low-protein diet during pregnancy. We further demonstrated that endorepellin significantly inhibited glomerular progenitor cell apoptosis which activates ERK1/2 phosphorylation. Our results show that endorepellin rescues the nephron number reduction in renal developmental programming, possibly through the inhibition of progenitor cell apoptosis via the ERK1/2 pathway. |
| first_indexed | 2024-04-11T19:39:50Z |
| format | Article |
| id | doaj.art-b804aced30d9468d8063713a2732b75c |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T19:39:50Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b804aced30d9468d8063713a2732b75c2022-12-22T04:06:45ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-10-011010.3389/fcell.2022.929556929556Protective role of endorepellin in renal developmental programmingXiaoshan Tang0Xiaoshan Tang1Manqing Sun2Manqing Sun3Qian Shen4Qian Shen5Jia Rao6Jia Rao7Xue Yang8Xue Yang9Ye Fang10Ye Fang11Tianchao Xiang12Tianchao Xiang13Shanshan Xue14Shanshan Xue15Lei Sun16Hong Xu17Hong Xu18Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaInstitute of Developmental Biology and Molecular Medicine, Fudan University, Shanghai, ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, ChinaAdverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major contributor to renal developmental programming. The differentially expressed protein perlecan, which we previously identified using proteomics, is an important extracellular matrix glycoprotein, and its domain V (endorepellin) can inhibit apoptosis through a paracrine form. In explanted mice embryonic metanephros, we found that endorepellin can rescue glomeruli-deficit phenotype resulting from malnutrition, and this protective effect was also verified in vivo using a renal developmental programming model which was given a low-protein diet during pregnancy. We further demonstrated that endorepellin significantly inhibited glomerular progenitor cell apoptosis which activates ERK1/2 phosphorylation. Our results show that endorepellin rescues the nephron number reduction in renal developmental programming, possibly through the inhibition of progenitor cell apoptosis via the ERK1/2 pathway.https://www.frontiersin.org/articles/10.3389/fcell.2022.929556/fullapopotosisintrauterine growth restrictionrenal developmentnephron endowmentendorepellin |
| spellingShingle | Xiaoshan Tang Xiaoshan Tang Manqing Sun Manqing Sun Qian Shen Qian Shen Jia Rao Jia Rao Xue Yang Xue Yang Ye Fang Ye Fang Tianchao Xiang Tianchao Xiang Shanshan Xue Shanshan Xue Lei Sun Hong Xu Hong Xu Protective role of endorepellin in renal developmental programming Frontiers in Cell and Developmental Biology apopotosis intrauterine growth restriction renal development nephron endowment endorepellin |
| title | Protective role of endorepellin in renal developmental programming |
| title_full | Protective role of endorepellin in renal developmental programming |
| title_fullStr | Protective role of endorepellin in renal developmental programming |
| title_full_unstemmed | Protective role of endorepellin in renal developmental programming |
| title_short | Protective role of endorepellin in renal developmental programming |
| title_sort | protective role of endorepellin in renal developmental programming |
| topic | apopotosis intrauterine growth restriction renal development nephron endowment endorepellin |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.929556/full |
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