Changes in cell fate determine the regenerative and functional capacity of the developing kidney before and after release of obstruction
| Autor: | Joseph C. Gigliotti, Vidya K. Nagalakshmi, R. Ariel Gomez, Frederick H. Epstein, Alexander L. Klibanov, Robert L. Chevalier, Maria Luisa S. Sequeira-Lopez, Soham Shah, Minghong Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Time Factors Mesenchyme Neovascularization Physiologic Mice Transgenic Hydronephrosis Nephron Kidney urologic and male genital diseases Article Renal Circulation 03 medical and health sciences medicine Animals Regeneration Cell Lineage Cell Proliferation Homeodomain Proteins urogenital system business.industry Gene Expression Regulation Developmental Cell Differentiation General Medicine medicine.disease Fibrosis Obstructive Nephropathy Disease Models Animal Oxidative Stress Phenotype 030104 developmental biology medicine.anatomical_structure Animals Newborn Cell Tracking Ureteric bud Renal blood flow Forkhead box D1 business Myofibroblast Signal Transduction Transcription Factors Ureteral Obstruction Kidney disease |
| Zdroj: | Clinical Science. 132:2519-2545 |
| ISSN: | 1470-8736 0143-5221 |
| Popis: | Congenital obstructive nephropathy is a major cause of chronic kidney disease (CKD) in children. The contribution of changes in the identity of renal cells to the pathology of obstructive nephropathy is poorly understood. Using a partial unilateral ureteral obstruction (pUUO) model in genetically modified neonatal mice, we traced the fate of cells derived from the renal stroma, cap mesenchyme, ureteric bud (UB) epithelium, and podocytes using Foxd1Cre, Six2Cre, HoxB7Cre, and Podocyte.Cre mice respectively, crossed with double fluorescent reporter (membrane-targetted tandem dimer Tomato (mT)/membrane-targetted GFP (mG)) mice. Persistent obstruction leads to a significant loss of tubular epithelium, rarefaction of the renal vasculature, and decreased renal blood flow (RBF). In addition, Forkhead Box D1 (Foxd1)-derived pericytes significantly expanded in the interstitial space, acquiring a myofibroblast phenotype. Degeneration of Sine Oculis Homeobox Homolog 2 (Six2) and HoxB7-derived cells resulted in significant loss of glomeruli, nephron tubules, and collecting ducts. Surgical release of obstruction resulted in striking regeneration of tubules, arterioles, interstitium accompanied by an increase in blood flow to the level of sham animals. Contralateral kidneys with remarkable compensatory response to kidney injury showed an increase in density of arteriolar branches. Deciphering the mechanisms involved in kidney repair and regeneration post relief of obstruction has potential therapeutic implications for infants and children and the growing number of adults suffering from CKD. |
| Databáze: | OpenAIRE |
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