Usage Information
Abstract
Accumulating evidence suggests the pathogenic role of immunity and metabolism in diabetic kidney disease (DKD). Herein, we aimed to investigate the effect of complement factor B (CFB) on lipid metabolism in the development of DKD. We found that in patients with diabetic nephropathy, the staining of Bb, CFB, C3a, C5a, and C5b-9 was markedly elevated in renal tubulointerstitium. Cfb-knockout diabetic mice had substantially milder tubulointerstitial injury and less ceramide biosynthesis. The in vitro study demonstrated that cytokine secretion, endoplasmic reticulum stress, oxidative stress, and cell apoptosis were ameliorated in HK-2 cells transfected with siRNA of CFB under high-glucose conditions. Exogenous ceramide supplementation attenuated the protective effect of CFB knockdown in HK-2 cells, while inhibiting ceramide synthases (CERS) with fumonisin B1 in CFB-overexpressing cells rescued the cell injury. CFB knockdown could downregulate the expression of NF-κB p65, which initiates the transcription of CERS3. Furthermore, C3 knockdown abolished CFB-mediated cytokine secretion, NF-κB signaling activation, and subsequently ceramide biosynthesis. Thus, CFB deficiency inhibited activation of the complement alternative pathway and attenuated kidney damage in DKD, especially tubulointerstitial injury, by inhibiting the NF-κB signaling pathway, further blocking the transcription of CERS, which regulates the biosynthesis of ceramide. CFB may be a promising therapeutic target of DKD.
Authors
Zi-jun Sun, Dong-yuan Chang, Min Chen, Ming-hui Zhao
Usage data is cumulative from March 2025 through March 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,387 | 547 |
| 160 | 161 | |
| Figure | 430 | 14 |
| Table | 113 | 0 |
| Supplemental data | 92 | 38 |
| Citation downloads | 83 | 0 |
| Totals | 2,265 | 760 |
| Total Views | 3,025 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
