Keratinocytes Releasable Factors Function as Anti-Fibrogenic Factors in vitro and in vivo

اولين كنگره بين المللي دانشجويي پزشكي سلولي و مولكولي

28 الي 30 بهمن 1389، شيراز - ايران

Presentation Type: Speech
Abstract:

Objective: Although, the promotion of healing in patients with non-healing wounds is desirable, over healing processes such as post-burn hypertrophic scarring (HSc) and keloid are both disfiguring and debilitating. Thus, an essential component of wound healing is its timely cessation. Without it, there can be a build up of excess and often a deleterious fibrotic condition. Termination of wound healing, therefore, requires a fine balance between some key matrix proteins such as collagen deposition and its hydrolysis. As such, like any other dynamic biological process, there must be a set of factors that gradually slow down and/or terminate the dynamic healing process at the late stage of wound healing. However, the nature of these factors is not known.
There are at least two sets of keratinocyte releasable factors that modulate the expression of key ECM such as collagen and MMPs in fibroblasts.
Materials and Method: Fibroblasts were either co-cultured with keratinocytes or received keratinocyte conditioned medium for a duration of 24 hr. Cells were then harvested and the expression of MMPs and type I collagen was evaluated by a specific microarray, northern blot and western blot analysis
Results: The findings revealed that Keratinocytes release two sets of ECM modulating factors that are important in controlling the healing process. One set of these factors that identified to be releasable form of stratifin and its isoforms increase the expression of MMP-1, 3, 8 and 24 in fibroblasts. While the second set of these factors reduce the expression of type I and type III collagen in fibroblasts. On the other hand, fibroblasts release some unknown factors that control the expression of keratinocyte derived anti-fibrogenic factors such as stratifin. These findings indicated that there exist a cross-talking between epithelial and fibroblasts and as such disruption of this interaction due to burn injury would lead to excessive accumulation of ECM which is characteristic feature of post-burn hypertrophic scarring.
Conclusion: Keratinocyte releasable factors control the expression of key ECM in fibroblasts which is in favour of scar resolution. As such any delay in epithelialization frequently seen in burn patients would imbalance the synthesis and degradation of ECM and leading to development of post burn hypertrophic and keloid formation in these patients.

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