2. Academic Validation
  3. The role of C-C motif chemokine ligand 2 in the preservation of myogenic tone in the kidney microvasculature of Dahl Salt-Sensitive rats

The role of C-C motif chemokine ligand 2 in the preservation of myogenic tone in the kidney microvasculature of Dahl Salt-Sensitive rats

  • Kidney Int. 2026 Jun;109(6):1155-1172. doi: 10.1016/j.kint.2026.02.019.
Wenguang Feng 1,  Zhengrong Guan 1,  Wei-Zhong Ying 1,  Conrad Feng 1,  Kelly A Hyndman 2,  Paul W Sanders 3
Affiliations

Affiliations

  • 1 Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • 2 Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • 3 Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Birmingham Veterans Affairs Health Care System, Birmingham, Alabama, USA. Electronic address: [email protected].
PMID: 41833640 DOI: 10.1016/j.kint.2026.02.019
Abstract

Introduction: Mechanisms of kidney injury in hypertension are incompletely understood. Here, we investigate the role of C-C motif chemokine ligand 2 (CCL2) in kidney microvascular function and hypertension-associated kidney injury using male Dahl salt-sensitive (SS) rats and SS rats lacking Ccl2 (SSCcl2-/-).

Methods: SS and SSCcl2-/- rats were examined to determine changes in blood pressure and kidney function with increased sodium chloride intake. Kidney microvasculature was examined for changes in expression of key regulatory contractile proteins and autoregulatory function in vivo and effects of CCL2 on function in vitro.

Results: SS, but not SSCcl2-/-, rats developed salt-dependent hypertension with loss of afferent arteriolar autoregulation and associated kidney injury. RNA-sequencing and Gene Set Enrichment Analysis of kidney microvessels showed upregulated expression of genes involved in smooth muscle contraction and the Notch3 pathway in SSCcl2-/- compared to SS rats on the same 0.3% sodium chloride diet. Key contractile proteins, Myosin light chain kinase (MLCK), phosphorylated Myosin light chain 2 (p-MLC2) and Myosin heavy chain 11, were reduced in the kidney microvasculature of SS rats but maintained in SSCcl2-/- rats. Kidney microvascular smooth muscle cells undergoing cyclic strain produced CCL2 that decreased expression of Notch3 and Myosin light chain kinase (Mylk). Addition of recombinant CCL2 to medium of kidney microvascular smooth muscle cells promoted dose-dependent decreases in mRNA expression of Notch3 and Mylk, and MLCK and p-MLC2 proteins.

Conclusions: CCL2 directly impairs kidney microvascular smooth muscle contractility, leading to autoregulatory dysfunction and kidney injury in hypertensive SS rats. The findings highlight CCL2 as a potential therapeutic target in hypertensive nephropathy.

Keywords

Dahl salt-sensitive rat; afferent arteriolar autoregulation; chemokines; hypertension; hypertension-associated nephropathy.

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