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Regulatory Mechanisms in Kidney Development and Function

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 May 2026 | Viewed by 431

Special Issue Editor


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Guest Editor
Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA
Interests: podocytes; junctions; foot processes; glomerulus; slit diaphragm; cytoskeleton; diabetes; focal segmental glomerular sclerosis; diabetic nephropathy

Special Issue Information

Dear Colleagues,

Development and function of the kidney is governed by conserved regulatory networks combining signaling pathways and transcriptional hierarchies. The molecular mechanisms of nephrogenesis exhibit both species-specific and conserved dynamics, with disruptions in many developmental mechanisms directly linked to renal diseases. Recent discoveries, method advancements, translational and pharmaceutical improvements have aided the nephrology community in understanding the mechanisms of kidney development, function, and disease implications. Joint efforts that bridge disciplines have blazed an understanding in cell type-specific expression profiles, gene discovery, and novel biomarkers of health and injury. The culmination of large-scale -omic technologies has created new avenues for research that are still being uncovered. The focus of this Special Issue is to assemble recent developments and cutting-edge research on regulatory mechanisms of kidney development and function for illuminating groundbreaking advancements.

Dr. Gary F. Gerlach
Guest Editor

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Keywords

  • drosophila nephrocyte
  • zebrafish pronephros
  • mesonephros
  • murine nephrogenesis
  • slit diaphragm
  • podocytes
  • junctions
  • tubule
  • mesenchymal-to-epithelia transition (MET)
  • epithelial-to-mesenchymal transition (EMT)
  • tubule segmentation
  • transcription factors
  • signaling pathways
  • foot processes
  • cytoskeleton
  • brush boarder
  • intercalated cells
  • renin angiotensin
  • diabetic kidney disease
  • podocytopathies
  • FSGS
  • minimal change disease
  • IgAN

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Published Papers (1 paper)

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Research

13 pages, 2963 KB  
Article
Vitamin D Deficiency Activates Gdnf-Ret-pErk1/2 Signal and Induces Kidney Malformations in Mice
by Minghui Yu, Ningli Ye, Haixin Ju, Qianfan Miao, Chunyan Wang, Rufeng Dai, Jing Chen, Yihui Zhai, Lei Sun, Xiaohui Wu, Hong Xu and Qian Shen
Int. J. Mol. Sci. 2026, 27(7), 3042; https://doi.org/10.3390/ijms27073042 - 27 Mar 2026
Viewed by 143
Abstract
Congenital anomalies of the kidney and urinary tract (CAKUT) constitute the most common underlying cause of chronic kidney disease in pediatric populations. Maternal hypovitaminosis D links to mesoderm-related birth defects, leading to our hypothesis that maternal vitamin D deficiency (VDD) impairs renal development [...] Read more.
Congenital anomalies of the kidney and urinary tract (CAKUT) constitute the most common underlying cause of chronic kidney disease in pediatric populations. Maternal hypovitaminosis D links to mesoderm-related birth defects, leading to our hypothesis that maternal vitamin D deficiency (VDD) impairs renal development (a mesoderm-derived process) and induces offspring CAKUT. To investigate whether a low-vitamin D level can cause CAKUT, we used vitamin D-free diets to induce a maternal vitamin D deficiency mice model. The maternal vitamin D deficiency (VDD) mice models and normal vitamin D status (CON) were successfully established by administering a vitamin D-free or vitamin D-sufficient diet for 4 weeks prior to pregnancy. The overall incidence of CAKUT was significantly increased in VDD neonatal mice (19.4% vs. 2.44%; p = 0.0006), with a higher incidence of early duplicated budding in E11.5. E11.5 ureteric bud tissue revealed significantly increased activity of Gdnf-Ret-p-Erk1/2 signaling in the VDD group. In vivo intervention with the p-Erk1/2 antagonist U0126 in the pregnant VDD mice model at E10.5 improved CAKUT occurrence in offspring with p-Erk1/2 expression decreasing toward normal levels. Early metanephric ureteric bud H3K4me3 CUT&TAG analysis at E12.5 revealed chromatin activation patterns, which revealed that the downregulation of Hnf1β promoter region peaks was accompanied by reduced Hnf1β expression, and Robo2 promoter region peak was upregulated with increased Robo2 expression in the VDD group. Maternal vitamin D deficiency in mice significantly increased offspring CAKUT incidence. This phenotype was mediated by enhanced Gdnf-Ret-p-Erk1/2 signaling and reversed by p-Erk1/2 inhibition, with VDD inducing epigenetic remodeling of Hnf1β and Robo2 promoters. Full article
(This article belongs to the Special Issue Regulatory Mechanisms in Kidney Development and Function)
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