Developmental Origins of Kidney Disease and Targeted Therapeutics

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 12974

Special Issue Editors

Gallagher Family Associate Professor of Stem Cell Biology, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA
Interests: development; pattern formation; organogenesis; regeneration; stem cell biology; nephrogenesis; hematopoiesis
Special Issues, Collections and Topics in MDPI journals
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA

Special Issue Information

Dear Colleagues,

During vertebrate embryogenesis, kidneys contain progenitor populations which fuel the formation of nephrons and the collecting duct network. Alterations in these events can lead to various renal malformations. The formation of mature nephrons is particularly critical, as these structures are the core functional units of the kidney that cleanse the blood and maintain fluid homeostasis. The absence or perturbation of nephrogenesis can cause congenital birth defects. Postnatally, nephron damage can initiate devastating acute and/or chronic conditions. Nephron composition is complex where over a dozen differentiated cell types are organized in distinct regions, each performing specialized physiological roles. Single-cell sequencing technologies have aided in characterizing and tracking these nephron cell types during kidney ontogeny and disease progression. Furthermore, the ability to grow kidney organoids has provided a new opportunity to study nephrogenesis, model human diseases, and screen compounds in a personalized manner. Advancing our understanding of nephron development and disease dynamics will facilitate the identification of key biomarkers and breakthroughs in renal therapeutics. This Special Issue will provide an open access opportunity to publish research and review articles related to the in vivo and in vitro development of nephrons.

Dr. Rebecca A. Wingert
Dr. Brooke Chambers
Guest Editors

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Keywords

  • nephron
  • segmentation
  • organoid
  • renal stem cell
  • differentiation
  • CAKUT
  • acute kidney injury
  • chronic kidney disease

Published Papers (3 papers)

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Research

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16 pages, 2831 KiB  
Article
Chemokine (C-C Motif) Ligand 8 and Tubulo-Interstitial Injury in Chronic Kidney Disease
by Jangwook Lee, Yeonhee Lee, Kyu-Hong Kim, Dong-Ki Kim, Kwon-Wook Joo, Sung-Joon Shin, Yon-Su Kim and Seung-Hee Yang
Cells 2022, 11(4), 658; https://doi.org/10.3390/cells11040658 - 14 Feb 2022
Cited by 5 | Viewed by 1753
Abstract
Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney [...] Read more.
Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney fibrosis in CKD model. Serum levels and tissue expression of CCL8 significantly increased with advancing CKD stage, proteinuria level, and pathologic deterioration. In Western blot analysis of primary cultured human tubular epithelial cells after induction of fibrosis with rTGF-β, CCL8 was upregulated by rTGF-β treatment and the simultaneous treatment with anti-CCL8 mAb mitigated the rTGF-β-induced an increase in fibronectin and a decrease E-cadherin and BCL-2 protein levels. The antiapoptotic effect of the anti-CCL8 mAb was also demonstrated by Annexin V/propidium iodide staining assay. In qRT-PCR analysis, mRNA expression levels of the markers for fibrosis and apoptosis showed similar expression patterns to those observed by western blotting. The immunohistochemical analysis revealed CCL8 and fibrosis- and apoptosis-related markers significantly increased in the unilateral ureteral obstruction model, which agrees with our in vitro findings. In conclusion, CCL8 pathway is associated with increased risk of kidney fibrosis and that CCL8 blockade can ameliorate kidney fibrosis and apoptosis. Full article
(This article belongs to the Special Issue Developmental Origins of Kidney Disease and Targeted Therapeutics)
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14 pages, 3642 KiB  
Article
C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis
by Yi-Hsien Hsieh, Wen-Chien Wang, Tung-Wei Hung, Chu-Che Lee and Jen-Pi Tsai
Cells 2021, 10(12), 3345; https://doi.org/10.3390/cells10123345 - 29 Nov 2021
Cited by 6 | Viewed by 1829
Abstract
CCL17, a chemotactic cytokine produced by macrophages, is known to promote inflammatory and fibrotic effects in multiple organs, but its role in mediating renal fibrosis is unclear. In our study cohort of 234 chronic kidney disease (CKD) patients and 65 healthy controls, human [...] Read more.
CCL17, a chemotactic cytokine produced by macrophages, is known to promote inflammatory and fibrotic effects in multiple organs, but its role in mediating renal fibrosis is unclear. In our study cohort of 234 chronic kidney disease (CKD) patients and 65 healthy controls, human cytokine array analysis revealed elevated CCL17 expression in CKD that correlated negatively with renal function. The area under the receiver operating characteristic curve of CCL17 to predict the development of CKD stages 3b–5 was 0.644 (p < 0.001), with the optimal cut-off value of 415.3 ng/mL. In vitro over-expression of CCL17 in HK2 cells had no effect on cell viability, but increased cell motility and the expression of α-SMA, vimentin and collagen I, as shown by western blot analysis. In a unilateral ureteral obstruction (UUO) mouse model, we observed significantly increased interstitial fibrosis and renal tubule dilatation by Masson’s Trichrome and H&E staining, and markedly increased expression of CCL17, vimentin, collagen I, and α-SMA by IHC stain, qRTPCR, and western blotting. CCL17 induced renal fibrosis by promoting the epithelial-mesenchymal transition, resulting in ECM accumulation. CCL17 may be a useful biomarker for predicting the development of advanced CKD. Full article
(This article belongs to the Special Issue Developmental Origins of Kidney Disease and Targeted Therapeutics)
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Review

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21 pages, 2430 KiB  
Review
The “3Ds” of Growing Kidney Organoids: Advances in Nephron Development, Disease Modeling, and Drug Screening
by Brooke E. Chambers, Nicole E. Weaver and Rebecca A. Wingert
Cells 2023, 12(4), 549; https://doi.org/10.3390/cells12040549 - 08 Feb 2023
Cited by 9 | Viewed by 8300
Abstract
A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures that resemble the native kidney organ. These miniature kidney-like structures can also be derived from [...] Read more.
A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures that resemble the native kidney organ. These miniature kidney-like structures can also be derived from primary patient cells and thus provide simplified context to observe how mutations in kidney-disease-associated genes affect organogenesis and physiological function. In the past several years, advances in kidney organoid technologies have achieved the formation of renal organoids with enhanced numbers of specialized cell types, less heterogeneity, and more architectural complexity. Microfluidic bioreactor culture devices, single-cell transcriptomics, and bioinformatic analyses have accelerated the development of more sophisticated renal organoids and tailored them to become increasingly amenable to high-throughput experimentation. However, many significant challenges remain in realizing the use of kidney organoids for renal replacement therapies. This review presents an overview of the renal organoid field and selected highlights of recent cutting-edge kidney organoid research with a focus on embryonic development, modeling renal disease, and personalized drug screening. Full article
(This article belongs to the Special Issue Developmental Origins of Kidney Disease and Targeted Therapeutics)
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