Experimental Inhibition of Periostin Attenuates Kidney Fibrosis.

Abstract

BACKGROUND:

Periostin is responsible for tissue regeneration, fibrosis, and wound healing via its interaction with integrin. Recently, the role of periostin has been shown to contribute to fibrosis in chronic kidney disease. We investigated the role of periostin and the effect of periostin blockade in renal fibrogenesis.

METHODS:

We investigated the function of periostin in vivo in wild-type and periostin-null mice (Postn-KO) in a unilateral ureteral obstruction (UUO) model. For the in vitro experiments, primary cultured inner medullary collecting duct cells from the wild-type and Postn-KO mice were used.

RESULTS:

Periostin expression was strongly induced by UUO in the wild-type mice. UUO induced renal fibrosis and morphological changes in the obstructed kidney of wild-type mice, whereas global knockout of periostin reduced fibrosis induced by UUO and improved kidney structure. Fibrosis- and inflammation-related mRNA were significantly induced in the wild-type mice and were decreased in the Postn-KO mice. Additionally, α-smooth muscle actin expression was increased following the administration of recombinant periostin in vitro. The effect of periostin blockade was examined using 2 methods. The integrin blockade peptide decreased fibrosis-related gene expression in in vitro experiments. Anti-periostin polyclonal antibody attenuated renal fibrosis induced by UUO through changes in transforming growth factor-β signaling and the inflammatory and apoptotic pathways.

CONCLUSION:

Periostin is a marker of renal fibrosis and may augment the progression of fibrogenesis as an extracellular matrix protein. Periostin blockade effectively attenuated renal fibrogenesis. Thus, periostin inhibition may be a therapeutic strategy for the amelioration of renal disease progression.

• Authors: Jin Ho Hwang, Seung Hee Yang, Yong Chul Kim, Jin Hyuk Kim, Jung Nam An, Kyung Chul Moon, Yun Kyu Oh, Jae Yoon Park, Dong Ki Kim, Yon Su Kim, Chun Soo Lim, Jung Pyo Lee
• Journal: American journal of nephrology (Am J Nephrol) Vol. 46 Issue 6 Pg. 501-517 ( 2017) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 29268247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

• Biomarkers
• Cell Adhesion Molecules
• Cytokines
• Integrins
• Oligopeptides
• POSTN protein, human
• Postn protein, mouse
• Transforming Growth Factor beta
• arginyl-glycyl-aspartyl-serine

Topics

• Animals
• Biomarkers (metabolism)
• Cell Adhesion Molecules (antagonists & inhibitors, genetics, metabolism)
• Cells, Cultured
• Cytokines (metabolism)
• Glomerulonephritis, IGA (complications, metabolism, pathology)
• Humans
• Inflammation (metabolism)
• Integrins (antagonists & inhibitors, metabolism)
• Kidney (pathology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Nephrosclerosis (etiology, metabolism)
• Oligopeptides
• Transforming Growth Factor beta
• Ureteral Obstruction