Keratinocyte growth factor stimulates the recovery of epithelial structure and function in a mouse model of total parenteral nutrition

Yang, Hua; Wildhaber, Barbara E.; Tazuke, Yuko; Teitelbaum, Daniel H.

doi:10.1177/0148607102026006333

Cited by 28 publications

(21 citation statements)

References 40 publications

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“…It is possible that a cytokine imbalance prevails with administration of TPN, or with SBS, which may result in the observed altered expression of KGF. In recent studies, exogenous KGF reversed the villus atrophy observed in rodent starvation and TPN models (12,13,47,53). In our mouse TPN model, villus atrophy occurred simultaneous with a 2-fold decline in KGF mRNA expression.…”

Section: Discussionsupporting

confidence: 55%

Intestinal Intraepithelial Lymphocyte γδ-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse

Yang

Antony

Wildhaber

et al. 2004

The Journal of Immunology

115

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Keratinocyte growth factor (KGF) promotes intestinal epithelial growth. To understand the relevance of intraepithelial lymphocyte (IEL)-derived KGF expression on epithelial growth, we used a mouse model of villus atrophy by the administration of total parenteral nutrition, and a model of villus hypertrophy by the creation of a short bowel syndrome. KGF expression was confined to γδ-ΤCR+ IELs. IEL-derived KGF expression was highest in the crypts, somewhat less in the lower portion of villi, and markedly lower in the upper portion of villi. Total parenteral nutrition administration was associated with a down-regulation of IEL-derived KGF expression, and short bowel syndrome was associated with an up-regulation of IEL-derived KGF expression. In the absence of γδ-ΤCR+ IEL, using γδ−/− mice, intestinal epithelial cell proliferation decreased in control, and in both mucosal atrophy (22% decline) and mucosal hypertrophy (14%) models. These results show that KGF from IELs is an important factor for maintenance of intestinal epithelial cell proliferation and villus growth.

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Section: Discussionsupporting

confidence: 55%

Intestinal Intraepithelial Lymphocyte γδ-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse

Yang

Antony

Wildhaber

et al. 2004

The Journal of Immunology

115

View full text Add to dashboard Cite

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“…Protein was extracted from isolated IEL, and immunoblots performed using a Bio-Rad protein assay kit (Bio-Rad Laboratories, Hercules, CA) with standard methods. 33 Purified biotinylated anti-mouse ACE (R&D Systems, Inc., Mineapolis, MN) (at a concentration of 0.1 µg/ml diluted in blocking solution (Zymed Laboratories, Inc., San Francisco, CA) was used for ACE detection. This was followed by an application of horse radish peroxidase-streptavidin conjugate (1:5000 dilution; Zymed).…”

Section: Animal Modelmentioning

confidence: 99%

Intestinal intraepithelial lymphocyte derived angiotensin converting enzyme modulates epithelial cell apoptosis

et al. 2005

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“…IEL are a distinct population of T-lymphocytes that reside above the basement membrane and lie between ECs, which line the intestinal lumen. Previous studies have shown that IEL play an important role in the maintenance of the gut barrier function, and support intestinal EC growth through production of KGF [24,26]. In a reciprocal fashion, growth and function of IEL has been shown to be dependent on the expression of a series of cytokines, particularly interleukin-7 (IL-7), which is produced by ECs, predominately after they have differentiated into goblet cells [27,28].…”

Section: Introductionmentioning

confidence: 99%

Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection

et al. 2007

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Early intestinal adaptation after massive small bowel resection (SBR) is driven by increased epithelial cell (EC) proliferation. There is a clear clinical difference in the post-operative course of patients after the loss of proximal (P) compared to distal (D) small bowel. This study examined the effects of the site of SBR on post-resectional intestinal adaptation, and investigated the potential mechanisms involved. C57BL/6J mice (n = 7/group) underwent: (1) 60% P-SBR, (2) 60% D-SBR, (3) 60% mid (M)-SBR and (4) SHAM-operation (transection/reanastomosis). Mice were sacrificed at 7 days after surgery and ECs and adjacent mucosal lymphocytes (IELs) isolated. Adaptation was assessed in both jejunum and ileum by quantification of villus height, crypt depth, villus cell size, crypt cell size (microns), goblet cell number, and EC proliferation (%BrdU incorporation). Proliferation signalling pathways including keratinocyte growth factor (KGF)/KGFR(1), IL-7/IL-7R, and epidermal growth factor receptor (EGFR) were measured by RT-PCR. Expression of IL-7 was further analysed by immunofluorescence. Data were analyzed using ANOVA. All three SBR models led to significant increases in villus height, crypt depth, goblet cell numbers and EC proliferation rate when compared to respective SHAM groups. The strongest morphometric changes were found for jejunal segments after M-SBR and for ileal segments after P-SBR. Furthermore, morphometric analysis showed that at 1-week post-resection a tremendous increase in EC numbers occurred in jejunal villi (cell hyperplasia), whereas a significant increase in EC size predominated in ileal villi (cell hypertrophy). mRNA expression of KGF, KGFR(1), IL-7R, and EGFR showed a significant increase only after D-SBR, whereas IL-7 increased significantly after SBR in all investigated models, and this was confirmed by immunofluorescence studies. Early intestinal adaptation shows distinct differences depending on the site of SBR, and is predominately driven by cell hyperplasia in jejunal villi and cell hypertrophy in ileal villi. However, the exact mechanisms, which guide these signalling pathways are still unclear.

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Keratinocyte growth factor stimulates the recovery of epithelial structure and function in a mouse model of total parenteral nutrition

Abstract: KGF administration reversed many of the adverse epithelial changes associated with TPN administration. Additionally, KGF up-regulated epithelial KGF receptor expression. It is possible that KGF may have a therapeutic efficacy in patients who are receiving TPN.

Cited by 28 publications

References 40 publications

Intestinal Intraepithelial Lymphocyte γδ-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse

Intestinal Intraepithelial Lymphocyte γδ-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse

Intestinal intraepithelial lymphocyte derived angiotensin converting enzyme modulates epithelial cell apoptosis

Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection

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