Journal of Cell Communication and Signaling

, Volume 12, Issue 1, pp 379–388 | Cite as

Endoglin haploinsufficiency is associated with differential regulation of extracellular matrix production during skin fibrosis and cartilage repair in mice

  • Anas Alzahrani
  • Yoon Chi
  • Kenneth W. Finnson
  • Meryem Blati
  • Bertrand Lussier
  • Mohit Kapoor
  • Stephane Roy
  • Anie PhilipEmail author
Research Article


Transforming growth factor (TGF)-β is a multifunctional growth factor with potent pro-fibrotic effects. Endoglin is a TGF-β co-receptor that strongly regulates TGF-β signaling in a variety of cell types. Although aberrant regulation of TGF-β signaling is known to play a key role in fibrotic diseases such as scleroderma and impaired cartilage repair, the significance of endoglin function in regulating these processes is poorly understood. Here we examined whether endoglin haploinsufficiency regulates extracellular (ECM) protein expression and fibrotic responses during bleomycin induced skin fibrosis and surgically induced osteoarthritis, using endoglin-heterozygous (Eng+/−) mice and wild-type (Eng+/+) littermates. Skin fibrosis was induced by injecting mice intradermally with bleomycin or vehicle. Osteoarthritis was induced surgically by destabilization of medial meniscus. Dermal thickness, cartilage integrity and ECM protein expression were then determined. Eng+/− mice subjected to bleomycin challenge show a marked decrease in dermal thickness (P < 0.005) and reduced collagen content and decreased collagen I, fibronectin, alpha-smooth muscle actin levels as compared to Eng+/+ mice, both under basal and bleomycin treated conditions. Eng+/− mice undergoing surgically induced osteoarthritis show no differences in the degree of cartilage degradation, as compared to Eng+/+ mice, although chondrocytes isolated from Eng+/− display markedly enhanced collagen II levels. Our findings suggest that endoglin haploinsufficiency in mice ameliorates bleomycin-induced skin fibrosis suggesting that endoglin represents a pro-fibrotic factor in the mouse skin. However, endoglin haploinsufficiency does not protect these mice from surgically indiced cartilage degradation, demonstrating differential regulation of endoglin action during skin and cartilage repair.


Fibrosis, skin, cartilage, osteoarthritis Endoglin TGF-beta Scleroderma Systemic sclerosis Animal model 



This study was supported by a Canadian Institutes of Health Research (CIHR) operating grant (FRN13732) to AP, a Research Award to AA from the King AbdulAziz University, Jeddah, Saudi Arabia, and a PhD studentship award to YC from FRQS, Quebec.

Compliance with Ethical Standards

Conflicts of Interest

The authors have no conflicts of interest.


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Copyright information

© The International CCN Society 2018

Authors and Affiliations

  • Anas Alzahrani
    • 1
    • 2
  • Yoon Chi
    • 1
  • Kenneth W. Finnson
    • 1
  • Meryem Blati
    • 1
  • Bertrand Lussier
    • 3
  • Mohit Kapoor
    • 4
    • 5
  • Stephane Roy
    • 6
  • Anie Philip
    • 1
    Email author
  1. 1.Division of Plastic Surgery, Department of Surgery ResearchMcGill UniversityMontrealCanada
  2. 2.Department of Surgery, Vascular Surgery Division, Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia
  3. 3.Department of Clinical Sciences, Faculty of Veterinary MedicineUniversité de MontréalMontrealCanada
  4. 4.Osteoarthritis Research UnitUniversity of Montreal Hospital Research Centre (CRCHUM) Notre-Dame HospitalMontrealCanada
  5. 5.Department of Surgery and Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  6. 6.Département de Stomatologie, Faculté de Médecine dentaireUniversité de MontréalMontrealCanada

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