Characteristics of Neuropeptide-Containing Innervation, Tissue Remodeling, Growth, and Vascularity in Noses of Patients With Cleft Lip and Palate

Evija Balode (Coresponding Author), Māra Pilmane

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


OBJECTIVE: To detect the appearance and distribution of factors regulating remodeling, innervation, growth, and vascularity of the nasal tissue affected by cleft lip and palate (CLP).

DESIGN: Morphological analysis of human tissue.

SETTING: Cleft and craniofacial center.

PARTICIPANTS: Fifteen patients who underwent CLP rhinoplasty, 7 control patients.


MAIN OUTCOME MEASURES: Immunohistochemistry was performed with protein gene product (PGP) 9.5, transforming growth factor β1 (TGFβ1), vascular endothelial growth factor (VEGF), cluster of differentiation 34 (CD34), matrix metalloproteinase 2 (MMP2), MMP9, and tissue inhibitor of metalloproteinase 2 (TIMP2). The results were evaluated semiquantitatively. Spearman rank order correlation coefficient and Mann-Whitney U test were used for statistical analysis.

RESULTS: Cleft lip and palate-affected tissue revealed dense and loose connective tissue, adipose cells, and hyaline cartilage, along with numerous CD34-positive endotheliocytes and regions of VEGF-positive neoangiogenesis. We observed moderate to numerous PGP 9.5-positive nerve fibers. Transforming growth factor β1, MMP2, MMP9, and TIMP2 were found in cartilage and connective tissue. Cleft lip and palate-affected tissue compared to control samples showed a statistically significant difference in PGP 9.5 ( P = .006), VEGF ( P = .001), MMP2 ( P = .002), MMP9 ( P = .013), and TIMP2 ( P < .001) expression. We observed a strong, positive correlation between VEGF and MMP9 ( P = .027; r S = 0.705).

CONCLUSIONS: The moderate expression of TGFβ1 and increased distribution of VEGF, MMP2, MMP9, and TIMP2 demonstrate an active extracellular matrix remodeling and angiogenesis, performed by proteases. The cartilaginous septum of the nose is an example of balance between tissue degradation and its suppression, demonstrated by the relationship between MMPs and TIMPs and the presence of VEGF.

Original languageEnglish
Pages (from-to)948-956
Number of pages9
JournalCleft Palate-Craniofacial Journal
Issue number8
Publication statusPublished - 1 Aug 2020


  • facial morphology
  • nasal morphology
  • nonsyndromic clefting
  • nose
  • rhinoplasty

Field of Science*

  • 3.2 Clinical medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


Dive into the research topics of 'Characteristics of Neuropeptide-Containing Innervation, Tissue Remodeling, Growth, and Vascularity in Noses of Patients With Cleft Lip and Palate'. Together they form a unique fingerprint.

Cite this