Kidney Week

Abstract: TH-PO0225

Scavenger Receptor Splice Variant SR-BII Facilitates High-Fat Diet (HFD)-Induced Kidney and Liver Fibrosis Through Increased Peripheral Inflammation

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Souza, Ana C., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States

Ana C. Souza, MD, PhD

• Bocharov, Alexander V., National Institutes of Health, Bethesda, Maryland, United States

Alexander V. Bocharov, MD

• Vishnyakova, Tatyana, National Institutes of Health, Bethesda, Maryland, United States

Tatyana Vishnyakova, PhD

• Baranova, Irina, National Institutes of Health, Bethesda, Maryland, United States

Irina Baranova

• Chen, Zhigang, National Institutes of Health, Bethesda, Maryland, United States

Zhigang Chen, PhD

• Remaley, Alan T., National Heart Lung and Blood Institute, Bethesda, Maryland, United States

Alan T. Remaley, MD, PhD

• Yuen, Peter S.T., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States

Peter S.T. Yuen, PhD

• Eggerman, Thomas, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States

Thomas Eggerman, MD, PhD

• Star, Robert A., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States

Robert A. Star, MD

Background

SR-BII is a splice variant of the scavenger receptor gene SCARB1, with incompletely understood function. Both variants can bind various lipoproteins, including HDL, LDL and VLDL, and mediate selective neutral lipid uptake. Lipoprotein-derived cholesteryl ester/triacylglycerol accumulates in cellular lipid droplets (LDs) which are greatly increased in the livers of transgenic mice with pLiv-11-directed expression of either human SR-BI or SR-BII. We hypothesized that SR-BI/II could significantly affect the development of metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), potentially through lipid accumulation or by activating MAPKs.

Methods

MASH mice were fed a high fat diet (HFD); after 1 week, SR-BII but not SR-BI transgenic mice, had greatly increased liver macrophage infiltration but similar levels of LDs accumulation compared to WT mice. Then only SR-BII transgenic mice were further characterized for development of metabolic syndrome, inflammation, fibrosis and organ damage after 16 weeks of HFD.

Results

HFD-induced liver damage, measured by plasma ALT, AST and LDH levels, were 2-times higher in HFD-treated SR-BII transgenic than in WT mice. SR-BII transgenic mice developed liver fibrosis measured by immunofluorescent staining for alpha actin/desmin and histochemical staining. Surprisingly, kidney tubular damage (as defined by tubular epithelial swelling, loss of brush border, vacuolar degeneration, necrotic tubules, cast formation and desquamation) and kidney fibrosis by Masson's Trichrome staining was significantly higher in SR-BII tgn mice: p=0.0079 and p=0.0038, respectively. SR-BII transgenic mice did not develop type II diabetes, and had lower liver lipid accumulation, but did have more liver and kidney inflammation than WT mice.

Conclusion

We demonstrate that overexpression of SR-BII in the liver (and other organs) facilitates development of histologic MASH, surprisingly with kidney fibrosis also. We suggest that SR-BII has additional functions beyond a lipid-centric mechanism that leads to the development of both liver and kidney damage/fibrosis.

Funding

• NIDDK Support