TY - JOUR
T1 - Biomarkers and heterogeneous fibroblast phenotype associated with incisional hernia
AU - Thankam, Finosh G.
AU - Larsen, Nicholas K.
AU - Varghese, Ann
AU - Bui, Thao Nguyen
AU - Reilly, Matthew
AU - Fitzgibbons, Robert J.
AU - Agrawal, Devendra K.
N1 - Funding Information:
This research work was supported by NIH-NHLBI grants R01HL147662 and R01HL144125 of DK Agrawal and CU Surgery research funds to Dr. Fitzgibbons. The content of this original article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/9
Y1 - 2021/9
N2 - Development of incisional hernia (IH) is multifactorial but inflammation and abdominal wall ECM (extracellular matrix) disorganization are key pathological events. We investigated if the differential expression of fibroblast biomarkers reflects the cellular milieu and the dysregulated ECM in IH tissues. Expression of fibroblast biomarkers, including connective tissue growth factor, alpha-smooth muscle actin (α-SMA), CD34 (cluster of differentiation 34), cadherin-11 and fibroblast specific protein 1 (FSP1), was examined by histology and immunofluorescence in the hernial-fascial ring/neck tissue (HRT) and hernia sack tissue (HST) harvested from the patients undergoing hernia surgery and compared with normal fascia (FT) and peritoneum (PT) harvested from brain-dead healthy subjects undergoing organ procurement for transplantation. The H&E staining revealed alterations in tissue architecture, fibroblast morphology, and ECM organization in the IH tissues compared to control. The biomarker for undifferentiated fibroblasts, CD34, was significantly higher in HST and decreased in HRT than the respective FT and PT controls. Also, the findings revealed an increased level of CTGF (connective tissue growth factor) with decrease in α-SMA in both HRT and HST compared to the controls. In addition, an increased level of FSP1 (fibroblast specific protein 1) and cadherin-11 in HRT with decreased level in HST were observed relative to the respective controls (FT and PT). Hence, these findings support the heterogeneity of fibroblast population at the laparotomy site that could contribute to the development of IH. Understanding the mechanisms causing the phenotype switch of these fibroblasts would open novel strategies to prevent the development of IH following laparotomy.
AB - Development of incisional hernia (IH) is multifactorial but inflammation and abdominal wall ECM (extracellular matrix) disorganization are key pathological events. We investigated if the differential expression of fibroblast biomarkers reflects the cellular milieu and the dysregulated ECM in IH tissues. Expression of fibroblast biomarkers, including connective tissue growth factor, alpha-smooth muscle actin (α-SMA), CD34 (cluster of differentiation 34), cadherin-11 and fibroblast specific protein 1 (FSP1), was examined by histology and immunofluorescence in the hernial-fascial ring/neck tissue (HRT) and hernia sack tissue (HST) harvested from the patients undergoing hernia surgery and compared with normal fascia (FT) and peritoneum (PT) harvested from brain-dead healthy subjects undergoing organ procurement for transplantation. The H&E staining revealed alterations in tissue architecture, fibroblast morphology, and ECM organization in the IH tissues compared to control. The biomarker for undifferentiated fibroblasts, CD34, was significantly higher in HST and decreased in HRT than the respective FT and PT controls. Also, the findings revealed an increased level of CTGF (connective tissue growth factor) with decrease in α-SMA in both HRT and HST compared to the controls. In addition, an increased level of FSP1 (fibroblast specific protein 1) and cadherin-11 in HRT with decreased level in HST were observed relative to the respective controls (FT and PT). Hence, these findings support the heterogeneity of fibroblast population at the laparotomy site that could contribute to the development of IH. Understanding the mechanisms causing the phenotype switch of these fibroblasts would open novel strategies to prevent the development of IH following laparotomy.
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U2 - 10.1007/s11010-021-04166-6
DO - 10.1007/s11010-021-04166-6
M3 - Article
C2 - 33942219
AN - SCOPUS:85105314998
VL - 476
SP - 3353
EP - 3363
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
SN - 0300-8177
IS - 9
ER -