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Updated: Aug 27, 2026
Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle
Daina Lasaitiene1, Peter Friberg, Birgitta Sundelin
1Dept. of Physiology, Institute of Physiology and Pharmacology, Univ. of Gothenburg, Box 432, S-405 30 Gothenburg, Sweden. Daina.Lasaitiene@kidney.med.gu.se
Abstract:
Pharmacological interruption of angiotensin II type 1 (AT(1)) receptor signaling during nephrogenesis in rats perturbs renal tubular development. Perturbed tubulogenesis may contribute to long-term impairment of urinary concentrating ability, which is the main functional irreversible defect. The aim of this study was to further characterize tubular developmental deficits in neonatal rats, focusing on the thick ascending limb of Henle (TALH), known to undergo profound developmental changes and to be involved in urine-concentrating mechanisms. We have carried out immunohistochemistry and Western immunoblotting using antibodies directed against the major histocompatibility complex class II (MHC II) molecule and different TALH-specific markers, namely, cyclooxygenase-2 (COX-2), Tamm-Horsfall glycoprotein (THP), and the bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter (BSC-1/NKCC2). Immunohistochemistry demonstrated expression of MHC II, COX-2, THP, and BSC-1/NKCC2 proteins in normally developing TALH cells. The AT(1)-receptor antagonist losartan abolished MHC II expression exclusively in the developing TALH cells. Increased expression of COX-2 and THP was observed in the TALH cells of losartan-treated rats. Western immunoblotting confirmed increases in cortical and medullary COX-2 and THP abundance and revealed a decrease in cortical BSC-1/NKCC2 abundance in response to losartan treatment. We conclude that neonatal losartan treatment causes significant changes in the phenotype of the developing TALH in the rat.
Insights
Neonatal losartan treatment disrupts kidney development by altering the thick ascending limb of Henle (TALH). This impacts key proteins involved in urine concentration, potentially leading to long-term kidney dysfunction.
Area of Science:
- Nephrology
- Developmental Biology
- Pharmacology
Background:
- Angiotensin II type 1 (AT(1)) receptor signaling is crucial during kidney development (nephrogenesis).
- Interruption of this signaling pathway can impair renal tubular development and urinary concentrating ability.
- The thick ascending limb of Henle (TALH) is vital for concentrating urine and undergoes significant developmental changes.
Purpose of the Study:
- To investigate the effects of AT(1) receptor blockade on TALH development in neonatal rats.
- To characterize specific tubular developmental deficits induced by losartan treatment.
- To examine changes in TALH-specific markers and major histocompatibility complex class II (MHC II) expression.
Main Methods:
- Immunohistochemistry was used to detect protein expression of MHC II, cyclooxygenase-2 (COX-2), Tamm-Horsfall glycoprotein (THP), and Na(+)-K(+)-2Cl(-) cotransporter (BSC-1/NKCC2) in TALH cells.
- Western immunoblotting was employed to quantify the abundance of these proteins in kidney tissues.
- Rats were treated with the AT(1)-receptor antagonist losartan during the neonatal period.
Main Results:
- Losartan treatment abolished MHC II expression in developing TALH cells.
- Increased expression of COX-2 and THP was observed in the TALH of losartan-treated rats.
- Western blots confirmed increased COX-2 and THP, and decreased BSC-1/NKCC2 abundance in response to losartan.
Conclusions:
- Neonatal blockade of AT(1) receptor signaling by losartan significantly alters the phenotype of developing rat TALH cells.
- These changes in protein expression suggest a disruption of normal TALH development and function.
- Further research is needed to understand the long-term consequences of these developmental perturbations on kidney function.
