ADAMTS7-Mediated Complement Factor H Degradation Potentiates Complement Activation to Contributing to Renal Injuries.

ABSTRACT:

Background

The dysfunction of complement factor H (CFH), the main soluble complement negative regulator, potentiates various complement-induced renal injuries. However, insights into the underlying mechanism of CFH dysfunction remain limited. In this study, we investigated whether extracellular protease-mediated degradation accounts for CFH dysfunction in complement-mediated renal injuries.

Methods

An unbiased interactome of lupus mice kidneys identified CFH-binding protease. In vitro cleavage assay clarified CFH degradation. Pristane-induced SLE or renal ischemia-reperfusion (I/R) injury models were used in wild-type and ADAMTS7-/- mice.

Results

We identified the metalloprotease ADAMTS7 as a CFH-binding protein in lupus kidneys. Moreover, the upregulation of ADAMTS7

SUBMITTER: Ma Z 

PROVIDER: S-EPMC10103097 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature