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A Novel Role of Hyaluronan and Its Membrane Receptors, CD44 and RHAMM, in Obesity-Related Kidney Pathology

Bingxue Qi1,2, Vishal Musale1, Xiong Weng1

  • 1Division of Diabetes, Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.

Biomolecules
|November 27, 2025
PubMed

Insights

Obesity-related kidney pathology involves hyaluronan (HA) and its receptors CD44/RHAMM, contributing to kidney damage. Targeting HA-CD44/RHAMM pathways offers a novel therapeutic strategy for preventing chronic kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathology

Background:

  • Obesity-related kidney pathology (ORKP) is a significant global health concern, exacerbating diabetic nephropathy and increasing kidney cancer risk.
  • Current ORKP treatments are hampered by a limited understanding of its underlying disease mechanisms.
  • Hyaluronan (HA) and its receptors, CD44 and RHAMM, are implicated in various fibrotic conditions.

Purpose of the Study:

  • To investigate the role of hyaluronan (HA) and its membrane receptors, CD44 and RHAMM, in obesity-related kidney pathology (ORKP).
  • To elucidate the molecular pathways linking HA-CD44/RHAMM signaling to kidney damage in obesity.
  • To evaluate the therapeutic potential of targeting the HA-CD44/RHAMM axis in ORKP.

Main Methods:

  • Utilized in vivo models to assess the impact of obesity on kidney function and pathology.
  • Employed pharmacological and genetic ablation strategies to inhibit HA, CD44, or RHAMM.
  • Conducted in vitro studies using human kidney cells to explore the link between insulin resistance and extracellular matrix (ECM) remodeling.
  • Analyzed human kidney biopsy samples to correlate CD44/RHAMM expression with markers of kidney dysfunction.

Main Results:

  • Obesity significantly increases renal HA deposition and CD44/RHAMM expression, activating detrimental signaling pathways (TGF-β1/Smad2/3, P38/JNK MAPK, ROCK/ERK).
  • These pathways lead to glomerulopathy, tubular injury, inflammation, albuminuria, and elevated serum creatinine.
  • Pharmacological or genetic inhibition of HA, CD44, or RHAMM effectively reversed obesity-induced kidney pathologies in vivo.
  • Human kidney biopsies showed elevated CD44 and RHAMM in chronic kidney disease and diabetic nephropathy, correlating with dysfunction markers.

Conclusions:

  • Hyaluronan (HA), CD44, and RHAMM play a critical, detrimental role in obesity-related kidney pathology.
  • Targeting the HA-CD44/RHAMM axis presents a promising therapeutic strategy for ORKP.
  • This approach holds potential for preventing the progression to chronic kidney disease.
Keywords:
CD44RHAMMhyaluronaninsulin resistancekidneymiceobesity

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