Modulation and redistribution of proteinase inhibitor 8 (Serpinb8) during kidney regeneration.
BACKGROUND
The intracellular serpin, proteinase inhibitor 8 (PI8/Serpinb8), can inhibit furin, a prohormone convertase involved in inflammation, prohormone processing and extracellular matrix remodeling. Unilateral ureteral obstruction (UUO) is a well-characterized model of kidney disease associated with interstitial fibrosis, where recovery involves cellular proliferation and extracellular matrix remodeling. Given the presence of mouse PI8 (mPI8) in kidney, the UUO technique was used to investigate its potential role in kidney disease and regeneration.


METHODS
RT-PCR and in situ hybridization was used to assess PI8 mRNA in kidney sections. Immunohistochemistry was used to examine mPI8 distribution in normal kidney, and following reversal of UUO.


RESULTS
mPI8 mRNA was detected in whole kidney by RT-PCR, and by in situ hybridization in convoluted tubules of the renal cortex and medulla. In normal and control contralateral unobstructed kidneys, mPI8 was within the ascending limb and convoluted section of the distal tubules. PI8 distribution did not change in UUO kidney, but was significantly altered in reversed UUO kidney, appearing in regions containing nephrons undergoing remodeling. These included regenerating proximal and distal tubules and glomeruli.


CONCLUSIONS
mPI8 distribution alters during kidney regeneration, possibly to control a prohormone convertase involved in inflammation or tissue repair.
Gillard
Anneliese
A
Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.
Scarff
Kate
K
Loveland
Kate L
KL
Ricardo
Sharon D
SD
Bird
Phillip I
PI
D000818:Animals; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000201:enzymology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000378:metabolism*; D014018:Tissue Distribution; D014517:Ureteral Obstruction / Q000201:enzymology
C108403:SERPINB8 protein, human; D015843:Serpins