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SPARC-null mice exhibit accelerated cutaneous wound closure
Amy D Bradshaw1, May J Reed, E Helene Sage
1Department of Vascular Biology, The Hope Heart Institute, Seattle, Washington 98104, USA.
Abstract:
Expression of SPARC (secreted protein acidic and rich in cysteine; osteonectin, BM-40), an extracellular matrix (ECM) associated protein, is coincident with matrix remodeling. To further identify the functions of SPARC in vivo, we have made excisional wounds on the dorsa of SPARC-null and wild-type mice and monitored closure over time. A significant decrease in the size of the SPARC-null wounds, in comparison to that of wild-type, was observed at Day 4 and was maximal at Day 7. Although substantial differences in the percentage of proliferating cells were not apparent in SPARC-null relative to wild-type wounds, primary cultures of SPARC-null dermal fibroblasts displayed accelerated migration, relative to wild-type fibroblasts, in wound assays in vitro. Although the expression of collagen I mRNA in wounds, as measured by in situ hybridization (ISH), was not significantly different in SPARC-null vs wild-type mice, the collagen content of unwounded skin appeared to be substantially lower in the SPARC-null animals. By hydroxyproline analysis, the concentration of collagen in SPARC-null skin was found to be half that of wild-type skin. Moreover, we found an inverse correlation between the efficiency of collagen gel contraction by dermal fibroblasts and the concentration of collagen within the gel itself. We propose that the accelerated wound closure seen in SPARC-null dermis results from its decreased collagen content, a condition contributing to enhanced contractibility.
Insights
Secreted protein acidic and rich in cysteine (SPARC) deficiency accelerates wound closure in mice. This is due to reduced collagen content in SPARC-null skin, enhancing dermal fibroblast contractibility for faster healing.
Area of Science:
- Biochemistry
- Dermatology
- Extracellular Matrix Biology
Background:
- Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is an extracellular matrix (ECM) protein implicated in matrix remodeling.
- Understanding the in vivo functions of SPARC is crucial for elucidating its role in biological processes like wound healing.
Purpose of the Study:
- To investigate the role of SPARC in skin wound healing by comparing SPARC-null mice with wild-type controls.
- To analyze the impact of SPARC deficiency on wound closure rates, cellular proliferation, fibroblast migration, and collagen content.
Main Methods:
- Excisional wounds were created on SPARC-null and wild-type mice to monitor wound closure over time.
- In vitro wound assays were performed using primary cultures of SPARC-null and wild-type dermal fibroblasts to assess migration.
- Collagen content in unwounded skin was quantified using hydroxyproline analysis.
- Collagen gel contraction by dermal fibroblasts was evaluated to assess contractibility.
Main Results:
- SPARC-null mice exhibited significantly accelerated wound closure compared to wild-type mice, with maximal differences observed by Day 7.
- SPARC-null dermal fibroblasts demonstrated accelerated migration in vitro.
- SPARC-null skin had approximately half the collagen concentration compared to wild-type skin.
- An inverse correlation was found between dermal fibroblast collagen gel contraction efficiency and collagen concentration within the gel.
Conclusions:
- Accelerated wound closure in SPARC-null mice is attributed to decreased collagen content in the dermis.
- Reduced collagen levels enhance the contractibility of dermal fibroblasts, leading to more efficient wound healing.
- SPARC plays a significant role in regulating skin collagen content and influencing the mechanical properties of the dermis during wound repair.