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Curcumin targets CXCL16-mediated podocyte injury and lipid accumulation in diabetic kidney disease treatment
Ying Chen1,2, Jun Tao1, Yijun He3
1Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Abstract:
Among the complications of diabetes, diabetic kidney disease (DKD) frequently emerges, typified by the detrimental effects on renal function, manifesting through inflammation, dysregulated lipid metabolism, and harm to podocytes. Existing research underscores the significance of the soluble form of C-X-C chemokine ligand 16 (CXCL16) within the context of renal impairments. However, whether CXCL16 is involved in the pathogenesis of DKD remains elusive. We report that CXCL16 levels in the serum and kidneys of individuals with DKD were elevated and correlated with various lipid parameters. The expression of CXCL16 in human podocytes subjected to high glucose or palmitic acid induction and exogenous CXCL16 administration in these cells were examined. Higher CXCL16 levels were linked to abnormal lipid metabolism. Exogenous CXCL16 administration induced lipid droplets, microfilament disorganization, apoptosis, oxidative stress, and inflammation, inhibited PPAR γ, up-regulated COX2 expression, and inhibited Nrf2 translocation in podocytes. Molecular analysis revealed that Curcumin (Cur), a polyphenolic compound derived from Curcuma longa and an Nrf2 agonist, targets the ATP-binding pocket of CXCL16, inhibiting its kinase activity. Meanwhile, Cur therapy alleviated podocyte injury, lipid accumulation, improved glomerulopathy, and reduced albuminuria. Furthermore, after silencing CXCL16 expression in podocytes using siRNA, the effects of exogenous CXCL16 were nullified, and Cur no longer exhibited any significant impact. Thus, CXCL16 participates in the pathogenesis of DKD. Inhibition of CXCL16 has shown promising results in experimental models, suggesting its beneficial effects in ameliorating DKD.
Insights
Soluble C-X-C chemokine ligand 16 (CXCL16) is elevated in diabetic kidney disease (DKD) and drives disease progression by promoting lipid accumulation and inflammation in podocytes. Curcumin therapy targeting CXCL16 shows promise for treating DKD.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetic kidney disease (DKD) is a major diabetes complication affecting renal function.
- The role of soluble C-X-C chemokine ligand 16 (CXCL16) in DKD pathogenesis is not well understood.
- CXCL16 is implicated in various renal impairments.
Purpose of the Study:
- To investigate the role of CXCL16 in the pathogenesis of diabetic kidney disease (DKD).
- To explore the therapeutic potential of Curcumin (Cur) by targeting CXCL16 in DKD.
Main Methods:
- Measured CXCL16 levels in serum and kidney tissues of DKD patients.
- Examined CXCL16 expression in human podocytes under high glucose/palmitic acid conditions.
- Administered exogenous CXCL16 and Curcumin to podocytes.
- Utilized siRNA to silence CXCL16 expression.
- Assessed podocyte injury, lipid metabolism, oxidative stress, inflammation, and Nrf2 translocation.
Main Results:
- CXCL16 levels were elevated in DKD patients and correlated with lipid parameters.
- Exogenous CXCL16 induced podocyte injury, lipid accumulation, inflammation, and oxidative stress.
- Curcumin inhibited CXCL16 kinase activity, alleviating podocyte injury and DKD markers.
- Silencing CXCL16 abolished the effects of exogenous CXCL16 and Curcumin.
Conclusions:
- CXCL16 plays a significant role in the pathogenesis of diabetic kidney disease (DKD).
- Targeting CXCL16 with Curcumin demonstrates therapeutic potential for ameliorating DKD.
- CXCL16 inhibition offers a promising strategy for managing DKD complications.
