Stellate cell-specific adhesion molecule protocadherin 7 regulates sinusoidal contraction

Area of Science:

• Cell Biology
• Hepatology
• Molecular Biology

Background:

• Chronic liver disease involves sustained inflammation and hepatocyte injury.
• Activated hepatic stellate cells (HSCs) transdifferentiate into fibrogenic myofibroblasts.
• Protocadherin 7 (PCDH7) is a cadherin family member with restricted expression in HSCs, previously uncharacterized in the liver.

Purpose of the Study:

• To investigate the role of protocadherin 7 (PCDH7) in hepatic stellate cell (HSC) function.
• To determine PCDH7's involvement in HSC contractility and its impact on liver sinusoidal tone.

Main Methods:

• Generated HSC-specific PCDH7 knockout mouse models.
• Utilized intravital multiphoton microscopy to assess HSC contraction in vivo.
• Established PCDH7-null HSC lines for in vitro contractility assays.
• Analyzed gene expression pathways related to adhesion and vasoregulation.

Main Results:

• Hepatic PCDH7 expression was confirmed to be strictly restricted to HSCs.
• HSC-specific PCDH7 knockout abrogated HSC-mediated sinusoidal contraction.
• Loss of PCDH7 in cultured HSCs significantly attenuated contractility and altered gene expression.
• Impaired Rho-GTPase signaling, reduced F-actin assembly, and loss of focal adhesions were observed in PCDH7 knockout cells.

Conclusions:

• Protocadherin 7 (PCDH7) is a novel, stellate cell-specific regulator of HSC contractility.
• PCDH7 deficiency results in cytoskeletal remodeling and sinusoidal relaxation.
• PCDH7 plays a critical role in maintaining HSC contractility and sinusoidal tone.