Citrullination preferentially proceeds in glomerular Bowman's capsule and increases in obstructive nephropathy

Area of Science:

• Biochemistry
• Nephrology
• Enzymology

Background:

• Peptidylarginine deiminases (PADs) are enzymes catalyzing protein citrullination, altering protein structure by removing positive charges.
• Citrullination modifies arginine residues to citrulline, impacting protein function and cellular processes.
• The role of PADs in kidney physiology and pathology remained largely unexplored.

Purpose of the Study:

• To investigate the expression and function of PADs in the kidney.
• To determine the specific type of PAD expressed in renal tissue.
• To examine the changes in PAD expression and protein citrullination during kidney injury.

Main Methods:

• Unilateral ureteral obstruction (UUO) model in male rats to induce kidney injury.
• Analysis of PAD expression using reverse transcription-polymerase chain reaction (RT-PCR).
• Quantification of PAD type II and citrullinated proteins via Western blot and immunohistochemistry.
• Histological examination and proteome analysis to identify citrullinated proteins.

Main Results:

• Only PAD type II was detected in rat kidneys.
• UUO significantly increased PAD type II expression and citrullinated protein levels in obstructed kidneys.
• PAD type II and citrullinated proteins were localized to parietal epithelial cells within Bowman's capsule.
• Obstruction release attenuated PAD type II and citrullinated protein levels.
• Actin was identified as a citrullinated protein in the kidney.

Conclusions:

• PAD type II and citrullinated proteins are specific markers for Bowman's capsule in the kidney.
• Their increased expression in response to UUO suggests a role in kidney damage.
• These markers show promise for clarifying the mechanisms of kidney diseases.