Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis

Yi Ting Chen, Fan Chi Chang, Ching Fang Wu, Yu Hsiang Chou, Huan Lun Hsu, Wen Chih Chiang, Juqun Shen, Yung Ming Chen, Kwan Dun Wu, Tun Jun Tsai, Jeremy S. Duffield, Shuei Liong Lin

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

Pericytes are the major source of scar-producing myofibroblasts following kidney injury; however, the mechanisms of this transition are unclear. To clarify this, we examined Collagen 1 (α1)-green fluorescent protein (GFP) reporter mice (pericytes and myofibroblasts express GFP) following ureteral obstruction or ischemia-reperfusion injury and focused on the role of platelet-derived growth factor (PDGF)-receptor (PDGFR) signaling in these two different injury models. Pericyte proliferation was noted after injury with reactivation of α-smooth muscle actin expression, a marker of the myofibroblast phenotype. PDGF expression increased in injured tubules, endothelium, and macrophages after injury, whereas PDGFR subunits α and Β were expressed exclusively in interstitial GFP-labeled pericytes and myofibroblasts. When PDGFRα or PDGFRΒ activation was inhibited by receptor-specific antibody following injury, proliferation and differentiation of pericytes decreased. The antibodies also blunted the injury-induced transcription of PDGF, transforming growth factor Β1, and chemokine CCL2. They also reduced macrophage infiltration and fibrosis. Imatinib, a PDGFR tyrosine kinase inhibitor, attenuated pericyte proliferation and kidney fibrosis in both fibrogenic models. Thus, PDGFR signaling is involved in pericyte activation, proliferation, and differentiation into myofibroblasts during progressive kidney injury. Hence, pericytes may be a novel target to prevent kidney fibrosis by means of PDGFR signaling blockade.

Original languageEnglish
Pages (from-to)1170-1181
Number of pages12
JournalKidney International
Volume80
Issue number11
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

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Platelet-Derived Growth Factor Receptors
Pericytes
Myofibroblasts
Fibrosis
Kidney
Wounds and Injuries
Green Fluorescent Proteins
Platelet-Derived Growth Factor
Macrophages
Ureteral Obstruction
Antibodies
Chemokine CCL2
Transforming Growth Factors
Reperfusion Injury
Endothelium
Cicatrix
Smooth Muscle
Actins
Collagen
Phenotype

ASJC Scopus subject areas

  • Nephrology

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Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis. / Chen, Yi Ting; Chang, Fan Chi; Wu, Ching Fang; Chou, Yu Hsiang; Hsu, Huan Lun; Chiang, Wen Chih; Shen, Juqun; Chen, Yung Ming; Wu, Kwan Dun; Tsai, Tun Jun; Duffield, Jeremy S.; Lin, Shuei Liong.

In: Kidney International, Vol. 80, No. 11, 12.2011, p. 1170-1181.

Research output: Contribution to journalArticle

Chen, YT, Chang, FC, Wu, CF, Chou, YH, Hsu, HL, Chiang, WC, Shen, J, Chen, YM, Wu, KD, Tsai, TJ, Duffield, JS & Lin, SL 2011, 'Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis', Kidney International, vol. 80, no. 11, pp. 1170-1181. https://doi.org/10.1038/ki.2011.208
Chen, Yi Ting ; Chang, Fan Chi ; Wu, Ching Fang ; Chou, Yu Hsiang ; Hsu, Huan Lun ; Chiang, Wen Chih ; Shen, Juqun ; Chen, Yung Ming ; Wu, Kwan Dun ; Tsai, Tun Jun ; Duffield, Jeremy S. ; Lin, Shuei Liong. / Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis. In: Kidney International. 2011 ; Vol. 80, No. 11. pp. 1170-1181.
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