Related Experiment Video

Updated: Jul 7, 2026

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

Activated extracellular signal-regulated kinase correlates with cyst formation and transforming growth factor-beta

S Omori1, H Kitagawa, J Koike

  • 1Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.

Kidney International
|February 15, 2008
PubMed

Insights

Fetal kidney obstruction causes renal dysplasia and abnormal mitogen-activated protein kinase (MAPK) signaling. The extracellular signal-regulated kinase (ERK) pathway appears to drive cyst formation and fibrosis in obstructed fetal kidneys.

Area of Science:

  • Developmental biology
  • Nephrology
  • Molecular signaling

Background:

  • Human renal dysplasia is linked to urinary tract obstruction and aberrant mitogen-activated protein kinase (MAPK) signaling.
  • Understanding MAPK roles in fetal kidney development under obstruction is crucial.

Purpose of the Study:

  • To investigate renal responses and MAPK expression in fetal lamb kidneys with induced obstruction.
  • To elucidate the role of specific MAPK pathways, including ERK, in kidney development and disease.

Main Methods:

  • Fetal lambs underwent surgical obstruction of the urinary tract at gestation day 60.
  • Kidneys were harvested at intervals from 2 days to term (day 145) for analysis.
  • Immunohistochemistry was used to assess proliferation (Ki-67), fibrosis (TGF-beta), and MAPK (p38, P-ERK, JNK) expression.

Main Results:

  • Obstruction led to progressive dilation, cyst formation, and increased Ki-67 and TGF-beta expression in fetal kidneys.
  • p38 MAPK was found in tubules, P-ERK in ureteric buds/collecting ducts, and JNK emerged in tubules at term in control kidneys.
  • Obstructed kidneys showed p38 and P-ERK in cyst epithelia, while JNK was absent.

Conclusions:

  • ERK signaling correlates with proliferation and fibrosis markers in obstructed fetal kidneys.
  • ERK activation may play a significant role in cystogenesis and interstitial fibrosis in obstructive nephropathy.
  • MAPK pathway modulation presents a potential therapeutic target for congenital kidney diseases.

More Related Videos

Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis04:37

Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis

Published on: April 25, 2025

Assessing Urinary Tract Junction Obstruction Defects by Methylene Blue Dye Injection06:05

Assessing Urinary Tract Junction Obstruction Defects by Methylene Blue Dye Injection

Published on: October 12, 2017

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...