Usage Information
Citation Information: JCI Insight. 2024;9(11):e174775. https://doi.org/10.1172/jci.insight.174775.
Abstract
Portal hypertension (PHTN) is a severe complication of liver cirrhosis and is associated with intrahepatic sinusoidal remodeling induced by sinusoidal resistance and angiogenesis. Collagen type IV (COL4), a major component of basement membrane, forms in liver sinusoids upon chronic liver injury. However, the role, cellular source, and expression regulation of COL4 in liver diseases are unknown. Here, we examined how COL4 is produced and how it regulates sinusoidal remodeling in fibrosis and PHTN. Human cirrhotic liver sample RNA sequencing showed increased COL4 expression, which was further verified via immunofluorescence staining. Single-cell RNA sequencing identified liver sinusoidal endothelial cells (LSECs) as the predominant source of COL4 upregulation in mouse fibrotic liver. In addition, COL4 was upregulated in a TNF-α/NF-κB–dependent manner through an epigenetic mechanism in LSECs in vitro. Indeed, by utilizing a CRISPRi-dCas9-KRAB epigenome-editing approach, epigenetic repression of the enhancer-promoter interaction showed silencing of COL4 gene expression. LSEC-specific COL4 gene mutation or repression in vivo abrogated sinusoidal resistance and angiogenesis, which thereby alleviated sinusoidal remodeling and PHTN. Our findings reveal that LSECs promote sinusoidal remodeling and PHTN during liver fibrosis through COL4 deposition.
Authors
Can Gan, Usman Yaqoob, Jianwen Lu, Man Xie, Abid Anwar, Nidhi Jalan-Sakrikar, Sofia Jerez, Tejasav S. Sehrawat, Amaia Navarro-Corcuera, Enis Kostallari, Nawras W. Habash, Sheng Cao, Vijay H. Shah
Usage data is cumulative from May 2024 through January 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,939 | 133 |
| 409 | 41 | |
| Figure | 462 | 3 |
| Supplemental data | 212 | 4 |
| Citation downloads | 72 | 0 |
| Totals | 3,094 | 181 |
| Total Views | 3,275 | |
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.
