2006
DOI: 10.1093/protein/gzj013
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Enhanced stability of recombinant keratinocyte growth factor by mutagenesis

Abstract: Native sequence keratinocyte growth factor (KGF) is fairly unstable, as manifested by the loss of the monomeric native protein accompanied by the accumulation of aggregated species during storage at moderate temperatures. Several different types of analogs were generated and the storage stability of the protein assessed. In the first type of analog one or more of the five cysteinyl residues in KGF were replaced; in the second class the N-terminal residues that included the first disulfide bond were deleted. Bo… Show more

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Cited by 39 publications
(34 citation statements)
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“…However, its potential for protecting against airway epithelial injury has not been well characterised. Therefore, the aim of the present study was to investigate whether or not pretreatment with DN23-KGF or palifermin, which results in enhanced KGF protein stability [25], protects the airway epithelium against NA-induced acute airway injury in vivo. Three experimental approaches were used in addressing this question.…”
Section: Pre-treatment With Dn23-kgf Protects Clara Cells Against Napmentioning
confidence: 99%
See 1 more Smart Citation
“…However, its potential for protecting against airway epithelial injury has not been well characterised. Therefore, the aim of the present study was to investigate whether or not pretreatment with DN23-KGF or palifermin, which results in enhanced KGF protein stability [25], protects the airway epithelium against NA-induced acute airway injury in vivo. Three experimental approaches were used in addressing this question.…”
Section: Pre-treatment With Dn23-kgf Protects Clara Cells Against Napmentioning
confidence: 99%
“…Human CYP2F1 exhibits 80% homology with mouse CYP2F2 and is also expressed in the respiratory tract [24]. Therefore, it was hypothesised that pre-treatment of lungs with N-terminally truncated recombinant human KGF (DN23-KGF; palifermin), which is characterised by enhanced protein stability [25], protects against NA-induced acute Clara cell damage of the murine distal airways. In order to address this question, four experimental approaches were used: 1) distal airways from mice pre-treated with DN23-KGF or PBS were isolated by microdissection [26] and analysed for cell membrane integrity, cell proliferation and Clara cell number following NA-induced injury; 2) serial noninvasive lung function analysis was performed in unanaesthetised mice by means of head-out body plethysmography [27] in order to assess the functional relevance of NA-induced acute airway injury and the potential protective effect of DN23-KGF at the organ level; 3) the effect of KGF treatment on mRNA expression of CYP2F2, which catalyses the conversion of NA into its cytotoxic 1R,2S-oxide [12], was analysed in microdissected distal airways, as well as in Clara cell-enriched pulmonary epithelial cells isolated from mouse lungs; and 4) mice were therapeutically treated with DN23-KGF at different time-points following the injection of NA in order to test the hypothesis that the protective effect of KGF treatment was dependent upon the presence of Clara cells.…”
mentioning
confidence: 99%
“…Platelet-derived growth factor is a dimeric protein held together by two disulfide bonds, which are essential for correct folding and stability of the protein (Ostman et al, 1993). The native monomeric sequence of the KGF has been shown to be unstable in plasma due to aggregation even at moderate storage temperatures (Hsu et al, 2006). Members of the FGF family have a short half-life in vivo due to denaturation at temperatures close to physiological (Zakrzewska et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…We also injected mice with KGF or vehicle control and compared CK5ϩ and Collagen1ϩ cell populations in the buffy coat 6 h after the injections (n ϭ 5). The recombinant human KGF, which has the native KGF sequence, has a half life of about half a day (31).…”
Section: Mobilization Of Cepcmentioning
confidence: 99%