Epithelial injury repair

Fibrotic disease results from epithelial injury and abnormal wound repair in the absence of preceding inflammation. 

Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, McMahon AP, Bonventre JV. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell 2008 2 284-291. 

Eosinophil Major Basic Protein 195 7. Repair of Epithelial Injury 199... 

Relationship of alveolar epithelial injury and repair to the induction of pulmonary fibrosis. Am. J. Pathol. 130 377-83... 

The role of the CO/HO axis in the control of cell proliferation and differentiation is still very poorly explored. Likewise, wound healing and tissue regeneration are two scientific niches where CO must be studied with much attention. There are few data about the role of CO on cellular proliferation/differentiation and most of the published data concern HO activity. HO-1 and HO-2 are involved in cornea wound healing HO-1 induction accelerates wound healing after epithelial injury [96] and deletion of HO-2 impairs re-epitheliaUzation delaying the repair response [97]. In the hepatic model, mice treated with CO presented higher levels of hepatocytic proliferation and enhanced expression of hepatocyte growth factor (HGF) after hepatectomy [98]. 

Tissue repair is a very important process in eye irritation, particularly corneal lesions, but has rarely been studied. Epithelial migration and proliferation are the primary events occurring after epithelial injury. It has been shown that fibronectin stimulates epithelial cell migration, whereas hyaluronic acid is more active on proliferation (Salonen et aL, 1991 Inoue and Katakami, 1993). Growth factors (EGF, FGF, etc.) have also been shown to play a role in corneal epithelial and endothelial wound healing (Dabin and Courtois, 1991 Raphael et al. 1993 Hoppenreijs et al., 1994). The effects of chemicals on the synthesis of these components by corneal cells could be extremely important in the modulation of repair processes. 

McElroy, M.C., and M. Kasper. 2004. The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair. Eur. Respir. J. 24 664-673. 

Lopez BD, Ubels JL (1991) Quantitative evaluation of the corneal epithelial barrier effect of artificial tears and preservatives. Curr Eye Res 10(7) 645-656 Rein M (2003) The ocular surface barrier function and mechanisms of injury and repair. In Salem H, Katz S (eds) Alternative Toxicological Methods. CRC Press, New York, pp 89-108... 

Figure 3. Proposed mechanism of renal cell repair and regeneration. Healthy renal epithelia are differentiated, quiescent columnar epitheiia. After injury, numerous renal cells die via necrosis and apoptosis depending on the level of insult. However a few cells are sublethally injured and lose cell polarity and many physiological functions. These cells can either initiate the repair process immediately or dedifferentiate into mesenchymal-like cells. Sublethally injured epithelial cells begin to migrate and proliferate to fill in denuded regions of the tubular lumen. The epithelial cells finally redifferentiate back into quiescent tubular cells and regain their polarity and physiological functions.

The process of wound healing after thermal injury (e.g. from laser treatment) involves re-epithelialization that starts within the first few hours after injury and continues throughout the different proliferative phases of skin repair. Viable keratinocytes (Figure 3.2) that are at the edge of the wound and have not suffered lethal or sublethal heat shock... 

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