Limits...
Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

Voorwald FA, Marchi FA, Villacis RA, Alves CE, Toniollo GH, Amorim RL, Drigo SA, Rogatto SR - PLoS ONE (2015)

Bottom Line: Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array.In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals.This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Veterinary Clinic and Department of Surgery, São Paulo State University (UNESP), Jaboticabal, São Paulo, Brazil.

ABSTRACT
Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.

No MeSH data available.


Related in: MedlinePlus

IPA network analysis.(A-D) Top networks identified with IPA software for differentially expressed genes in different group’s comparisons: A-B: Pyometra compared with diestrus, CEH and mucometra. A: Family members of the MMP and S100 genes were detected as central nodes in pyometra and connected with pro-inflammatory cytokines. The SLP1 gene (highest fold change in pyometra) is also depicted. B: Multiple interactions between the CXCL8/IL8, a pro-inflammatory gene, and other genes are shown, including the PTGS2/COX2 gene. C-D: Pyometra of animals previously treated with progesterone compounds compared to pyometra of untreated dogs. C: The proinflammatory cytokine TNF was detected as central with multiple connections with different genes. D: E2F1 (overexpression) and VEGF (underexpression) products in the treated group. The lines between genes represent known interactions, with solid lines and dashed lines representing direct and indirect interactions, respectively. Different node shapes represent the functional class of the gene product. Red and green nodes represent overexpressed and underexpressed genes in each comparison.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4519320&req=5

pone.0133894.g002: IPA network analysis.(A-D) Top networks identified with IPA software for differentially expressed genes in different group’s comparisons: A-B: Pyometra compared with diestrus, CEH and mucometra. A: Family members of the MMP and S100 genes were detected as central nodes in pyometra and connected with pro-inflammatory cytokines. The SLP1 gene (highest fold change in pyometra) is also depicted. B: Multiple interactions between the CXCL8/IL8, a pro-inflammatory gene, and other genes are shown, including the PTGS2/COX2 gene. C-D: Pyometra of animals previously treated with progesterone compounds compared to pyometra of untreated dogs. C: The proinflammatory cytokine TNF was detected as central with multiple connections with different genes. D: E2F1 (overexpression) and VEGF (underexpression) products in the treated group. The lines between genes represent known interactions, with solid lines and dashed lines representing direct and indirect interactions, respectively. Different node shapes represent the functional class of the gene product. Red and green nodes represent overexpressed and underexpressed genes in each comparison.

Mentions: Canonical pathway and network analysis by IPA were performed for the differentially expressed genes in pyometra. Network analysis showed multiple interactions between the MMP genes and S100 family genes detected with the highest fold change (Fig 2A). In addition, important interactions between overexpressed CXCL8 gene, a chemokine that is one of the major mediators of the inflammatory response, and other genes were highlighted, including the PTGS2/COX2 gene (Fig 2B).


Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

Voorwald FA, Marchi FA, Villacis RA, Alves CE, Toniollo GH, Amorim RL, Drigo SA, Rogatto SR - PLoS ONE (2015)

IPA network analysis.(A-D) Top networks identified with IPA software for differentially expressed genes in different group’s comparisons: A-B: Pyometra compared with diestrus, CEH and mucometra. A: Family members of the MMP and S100 genes were detected as central nodes in pyometra and connected with pro-inflammatory cytokines. The SLP1 gene (highest fold change in pyometra) is also depicted. B: Multiple interactions between the CXCL8/IL8, a pro-inflammatory gene, and other genes are shown, including the PTGS2/COX2 gene. C-D: Pyometra of animals previously treated with progesterone compounds compared to pyometra of untreated dogs. C: The proinflammatory cytokine TNF was detected as central with multiple connections with different genes. D: E2F1 (overexpression) and VEGF (underexpression) products in the treated group. The lines between genes represent known interactions, with solid lines and dashed lines representing direct and indirect interactions, respectively. Different node shapes represent the functional class of the gene product. Red and green nodes represent overexpressed and underexpressed genes in each comparison.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519320&req=5

pone.0133894.g002: IPA network analysis.(A-D) Top networks identified with IPA software for differentially expressed genes in different group’s comparisons: A-B: Pyometra compared with diestrus, CEH and mucometra. A: Family members of the MMP and S100 genes were detected as central nodes in pyometra and connected with pro-inflammatory cytokines. The SLP1 gene (highest fold change in pyometra) is also depicted. B: Multiple interactions between the CXCL8/IL8, a pro-inflammatory gene, and other genes are shown, including the PTGS2/COX2 gene. C-D: Pyometra of animals previously treated with progesterone compounds compared to pyometra of untreated dogs. C: The proinflammatory cytokine TNF was detected as central with multiple connections with different genes. D: E2F1 (overexpression) and VEGF (underexpression) products in the treated group. The lines between genes represent known interactions, with solid lines and dashed lines representing direct and indirect interactions, respectively. Different node shapes represent the functional class of the gene product. Red and green nodes represent overexpressed and underexpressed genes in each comparison.
Mentions: Canonical pathway and network analysis by IPA were performed for the differentially expressed genes in pyometra. Network analysis showed multiple interactions between the MMP genes and S100 family genes detected with the highest fold change (Fig 2A). In addition, important interactions between overexpressed CXCL8 gene, a chemokine that is one of the major mediators of the inflammatory response, and other genes were highlighted, including the PTGS2/COX2 gene (Fig 2B).

Bottom Line: Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array.In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals.This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Veterinary Clinic and Department of Surgery, São Paulo State University (UNESP), Jaboticabal, São Paulo, Brazil.

ABSTRACT
Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.

No MeSH data available.


Related in: MedlinePlus