Tsc1 ablation in Prx1 and Osterix lineages causes renal cystogenesis in mouse

Zhixiang Wu, Hongguang Wu, Shafiquzzaman Md, Guo Yu, Samy L Habib, Baojie Li, Jing Li

Research output: Contribution to journalArticle

Abstract

Tuberous Sclerosis Complex (TSC) is caused by mutations in TSC1 or TSC2, which encode negative regulators of the mTOR signaling pathway. The renal abnormalities associated with TSC include angiomyolipoma, cysts, and renal cell carcinoma. Here we report that specific ablation of Tsc1 using the mesenchymal stem cell-osteoblast lineage markers induced cystogenesis in mice. Using Rosa-tdTomato mice, we found that Prx1- or Dermo1-labeled cells were present in the nephron including glomerulus but they were not stained by markers for podocytes, mesangial cells, endothelial cells, or proximal or loop of Henle tubular cells, while Osx is known to label tubular cells. Tsc1 deficiency in Prx1 lineage cells caused development of mild cysts that were positive only for Tamm-Horsfall protein (THP), a loop of Henle marker, while Tsc1 deficiency in Osx lineage cells caused development of cysts that were positive for Villin, a proximal tubular cell marker. On the other hand, Tsc1 deficiency in the Dermo1 lineage did not produce detectable phenotypical changes in the kidney. Cyst formation in Prx1-Cre; Tsc1 f/f and Osx-Cre; Tsc1 f/f mice were associated with increase in both proliferative and apoptotic cells in the affected tissue and were largely suppressed by rapamycin. These results suggest that Prx1 and Osx lineages cells may contribute to renal cystogenesis in TSC patients.

Original languageEnglish (US)
Article number837
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Kidney
Tuberous Sclerosis
Cysts
Loop of Henle
Uromodulin
Angiomyolipoma
Podocytes
Mesangial Cells
Nephrons
Cell Lineage
Sirolimus
Osteoblasts
Mesenchymal Stromal Cells
Renal Cell Carcinoma
Endothelial Cells
Mutation

ASJC Scopus subject areas

  • General

Cite this

Tsc1 ablation in Prx1 and Osterix lineages causes renal cystogenesis in mouse. / Wu, Zhixiang; Wu, Hongguang; Md, Shafiquzzaman; Yu, Guo; Habib, Samy L; Li, Baojie; Li, Jing.

In: Scientific Reports, Vol. 9, No. 1, 837, 01.12.2019.

Research output: Contribution to journalArticle

Wu, Zhixiang ; Wu, Hongguang ; Md, Shafiquzzaman ; Yu, Guo ; Habib, Samy L ; Li, Baojie ; Li, Jing. / Tsc1 ablation in Prx1 and Osterix lineages causes renal cystogenesis in mouse. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
@article{4440068e85d247b8b42add64942b5379,
title = "Tsc1 ablation in Prx1 and Osterix lineages causes renal cystogenesis in mouse",
abstract = "Tuberous Sclerosis Complex (TSC) is caused by mutations in TSC1 or TSC2, which encode negative regulators of the mTOR signaling pathway. The renal abnormalities associated with TSC include angiomyolipoma, cysts, and renal cell carcinoma. Here we report that specific ablation of Tsc1 using the mesenchymal stem cell-osteoblast lineage markers induced cystogenesis in mice. Using Rosa-tdTomato mice, we found that Prx1- or Dermo1-labeled cells were present in the nephron including glomerulus but they were not stained by markers for podocytes, mesangial cells, endothelial cells, or proximal or loop of Henle tubular cells, while Osx is known to label tubular cells. Tsc1 deficiency in Prx1 lineage cells caused development of mild cysts that were positive only for Tamm-Horsfall protein (THP), a loop of Henle marker, while Tsc1 deficiency in Osx lineage cells caused development of cysts that were positive for Villin, a proximal tubular cell marker. On the other hand, Tsc1 deficiency in the Dermo1 lineage did not produce detectable phenotypical changes in the kidney. Cyst formation in Prx1-Cre; Tsc1 f/f and Osx-Cre; Tsc1 f/f mice were associated with increase in both proliferative and apoptotic cells in the affected tissue and were largely suppressed by rapamycin. These results suggest that Prx1 and Osx lineages cells may contribute to renal cystogenesis in TSC patients.",
author = "Zhixiang Wu and Hongguang Wu and Shafiquzzaman Md and Guo Yu and Habib, {Samy L} and Baojie Li and Jing Li",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-018-37139-9",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Tsc1 ablation in Prx1 and Osterix lineages causes renal cystogenesis in mouse

AU - Wu, Zhixiang

AU - Wu, Hongguang

AU - Md, Shafiquzzaman

AU - Yu, Guo

AU - Habib, Samy L

AU - Li, Baojie

AU - Li, Jing

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Tuberous Sclerosis Complex (TSC) is caused by mutations in TSC1 or TSC2, which encode negative regulators of the mTOR signaling pathway. The renal abnormalities associated with TSC include angiomyolipoma, cysts, and renal cell carcinoma. Here we report that specific ablation of Tsc1 using the mesenchymal stem cell-osteoblast lineage markers induced cystogenesis in mice. Using Rosa-tdTomato mice, we found that Prx1- or Dermo1-labeled cells were present in the nephron including glomerulus but they were not stained by markers for podocytes, mesangial cells, endothelial cells, or proximal or loop of Henle tubular cells, while Osx is known to label tubular cells. Tsc1 deficiency in Prx1 lineage cells caused development of mild cysts that were positive only for Tamm-Horsfall protein (THP), a loop of Henle marker, while Tsc1 deficiency in Osx lineage cells caused development of cysts that were positive for Villin, a proximal tubular cell marker. On the other hand, Tsc1 deficiency in the Dermo1 lineage did not produce detectable phenotypical changes in the kidney. Cyst formation in Prx1-Cre; Tsc1 f/f and Osx-Cre; Tsc1 f/f mice were associated with increase in both proliferative and apoptotic cells in the affected tissue and were largely suppressed by rapamycin. These results suggest that Prx1 and Osx lineages cells may contribute to renal cystogenesis in TSC patients.

AB - Tuberous Sclerosis Complex (TSC) is caused by mutations in TSC1 or TSC2, which encode negative regulators of the mTOR signaling pathway. The renal abnormalities associated with TSC include angiomyolipoma, cysts, and renal cell carcinoma. Here we report that specific ablation of Tsc1 using the mesenchymal stem cell-osteoblast lineage markers induced cystogenesis in mice. Using Rosa-tdTomato mice, we found that Prx1- or Dermo1-labeled cells were present in the nephron including glomerulus but they were not stained by markers for podocytes, mesangial cells, endothelial cells, or proximal or loop of Henle tubular cells, while Osx is known to label tubular cells. Tsc1 deficiency in Prx1 lineage cells caused development of mild cysts that were positive only for Tamm-Horsfall protein (THP), a loop of Henle marker, while Tsc1 deficiency in Osx lineage cells caused development of cysts that were positive for Villin, a proximal tubular cell marker. On the other hand, Tsc1 deficiency in the Dermo1 lineage did not produce detectable phenotypical changes in the kidney. Cyst formation in Prx1-Cre; Tsc1 f/f and Osx-Cre; Tsc1 f/f mice were associated with increase in both proliferative and apoptotic cells in the affected tissue and were largely suppressed by rapamycin. These results suggest that Prx1 and Osx lineages cells may contribute to renal cystogenesis in TSC patients.

UR - http://www.scopus.com/inward/record.url?scp=85060751390&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060751390&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-37139-9

DO - 10.1038/s41598-018-37139-9

M3 - Article

C2 - 30696882

AN - SCOPUS:85060751390

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 837

ER -