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Gerarduzzi C, Kumar RK, Trivedi P, et al. Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation. JCI Insight. 2017;2(8)doi: 10.1172/jci.insight.90299.
Gerarduzzi, C., Kumar, R. K., Trivedi, P., Ajay, A. K., Iyer, A., Boswell, S., Hutchinson, J. N., Waikar, S. S., & Vaidya, V. S. (2017). Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation. JCI insight, 2(8), . https://doi.org/10.1172/jci.insight.90299
Gerarduzzi, Casimiro, et al. "Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation." JCI insight vol. 2,8 (2017). doi: https://doi.org/10.1172/jci.insight.90299
Gerarduzzi C, Kumar RK, Trivedi P, Ajay AK, Iyer A, Boswell S, Hutchinson JN, Waikar SS, Vaidya VS. Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation. JCI Insight. 2017 Apr 20;2(8). doi: 10.1172/jci.insight.90299. eCollection 2017 Apr 20. PMID: 28422762; PMCID: PMC5396522.
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JCI Insight. 2017 Apr 20;2(8). doi: 10.1172/jci.insight.90299. eCollection 2017 Apr 20.

Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to myofibroblast transformation.

JCI insight

Casimiro Gerarduzzi, Ramya K Kumar, Priyanka Trivedi, Amrendra K Ajay, Ashwin Iyer, Sarah Boswell, John N Hutchinson, Sushrut S Waikar, Vishal S Vaidya

Affiliations

  1. Renal Division, Department of Medicine, Brigham and Women's Hospital (BWH), Boston, Massachusetts, USA.
  2. Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, Massachusetts, USA.
  3. Department of Biostatistics.
  4. Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.

PMID: 28422762 PMCID: PMC5396522 DOI: 10.1172/jci.insight.90299

Abstract

Secreted modular calcium-binding protein 2 (SMOC2) belongs to the secreted protein acidic and rich in cysteine (SPARC) family of matricellular proteins whose members are known to modulate cell-matrix interactions. We report that SMOC2 is upregulated in the kidney tubular epithelial cells of mice and humans following fibrosis. Using genetically manipulated mice with SMOC2 overexpression or knockdown, we show that SMOC2 is critically involved in the progression of kidney fibrosis. Mechanistically, we found that SMOC2 activates a fibroblast-to-myofibroblast transition (FMT) to stimulate stress fiber formation, proliferation, migration, and extracellular matrix production. Furthermore, we demonstrate that targeting SMOC2 by siRNA results in attenuation of TGFβ1-mediated FMT in vitro and an amelioration of kidney fibrosis in mice. These findings implicate that SMOC2 is a key signaling molecule in the pathological secretome of a damaged kidney and targeting SMOC2 offers a therapeutic strategy for inhibiting FMT-mediated kidney fibrosis - an unmet medical need.

Keywords: Nephrology

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