TY - JOUR
T1 - Extracellular matrix analysis of fibrosis
T2 - A step towards tissue engineering for urethral stricture disease
AU - Linssen, Emma C
AU - Demmers, Jeroen
AU - van Dijk, Christian G M
AU - van Dam, Roos
AU - Nicese, Maria Novella
AU - Cheng, Caroline
AU - de Kort, Laetitia M O
AU - de Graaf, Petra
N1 - Publisher Copyright:
Copyright: © 2023 Linssen et al.
PY - 2023/11
Y1 - 2023/11
N2 - The urogenital tract is a target for many congenital and acquired diseases, both benign and oncogenic. In males, the urethra that transports urine and semen can be obstructed by a fibrotic disease called urethral stricture disease (USD). In severe USD, the whole organ including the vascular embedding, the corpus spongiosum (CS), is affected. Recurrent or severe USD is treated by reconstructive surgery. Tissue engineering may improve the outcome of urethral reconstruction in patients with complicated USD. Currently in urethral reconstruction only the epithelial layer is replaced, no substitution for the CS is provided, while the CS is important for mechanical support and vascularization. To develop a tissue engineering strategy for the CS, it is necessary to know the protein composition of the CS. As the extracellular matrix (ECM) plays an important role in the formation of fibrosis, we analyzed the distribution and localization of ECM components in human healthy and fibrotic CS tissue using immunohistology. The morphology of components of the elastic network were affected in USD. After decellularization a clear enrichment of proteins belonging to the ECM was found. In the proteomic analysis collagens COL15A1 and COL4A2 as well as inter-alpha-trypsin inhibitor ITIH4 were upregulated in fibrotic samples. The glycoproteins Periostin (POSTN), Microfibrillar-associated protein 5 (MFAP5) and EMILIN2 are downregulated in fibrotic tissue. To our knowledge this is the first proteomic study of ECM proteins of the CS in healthy and in USD. With these results a regenerating approach for tissue engineered CS can be developed, including relevant ECM proteins that reduce fibrosis and promote healthy healing in urethral reconstructive surgery.
AB - The urogenital tract is a target for many congenital and acquired diseases, both benign and oncogenic. In males, the urethra that transports urine and semen can be obstructed by a fibrotic disease called urethral stricture disease (USD). In severe USD, the whole organ including the vascular embedding, the corpus spongiosum (CS), is affected. Recurrent or severe USD is treated by reconstructive surgery. Tissue engineering may improve the outcome of urethral reconstruction in patients with complicated USD. Currently in urethral reconstruction only the epithelial layer is replaced, no substitution for the CS is provided, while the CS is important for mechanical support and vascularization. To develop a tissue engineering strategy for the CS, it is necessary to know the protein composition of the CS. As the extracellular matrix (ECM) plays an important role in the formation of fibrosis, we analyzed the distribution and localization of ECM components in human healthy and fibrotic CS tissue using immunohistology. The morphology of components of the elastic network were affected in USD. After decellularization a clear enrichment of proteins belonging to the ECM was found. In the proteomic analysis collagens COL15A1 and COL4A2 as well as inter-alpha-trypsin inhibitor ITIH4 were upregulated in fibrotic samples. The glycoproteins Periostin (POSTN), Microfibrillar-associated protein 5 (MFAP5) and EMILIN2 are downregulated in fibrotic tissue. To our knowledge this is the first proteomic study of ECM proteins of the CS in healthy and in USD. With these results a regenerating approach for tissue engineered CS can be developed, including relevant ECM proteins that reduce fibrosis and promote healthy healing in urethral reconstructive surgery.
KW - Extracellular Matrix Proteins
KW - Extracellular Matrix/pathology
KW - Fibrosis
KW - Humans
KW - Male
KW - Proteomics
KW - Tissue Engineering/methods
KW - Urethra/pathology
KW - Urethral Stricture/surgery
UR - http://www.scopus.com/inward/record.url?scp=85178513322&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0294955
DO - 10.1371/journal.pone.0294955
M3 - Article
C2 - 38032942
SN - 1932-6203
VL - 18
JO - PLoS ONE
JF - PLoS ONE
IS - 11 November
M1 - e0294955
ER -