Biomarkers and heterogeneous fibroblast phenotype associated with incisional hernia

Finosh G. Thankam,Nicholas K. Larsen,Thao-Nguyen Bui,Devendra K. Agrawal,Ann Varghese,Robert J. Fitzgibbons,Matthew Reilly

doi:10.1007/s11010-021-04166-6

Abstract

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.

Highlights

The incidence of incisional hernia (IH) following a laparotomy is on average reported to be between 10–20% but is much higher in certain subpopulations such as those undergoing a colectomy for diverticulitis [1] [2]
The findings revealed an increased level of connective tissue growth factor (CTGF) with decrease in α-smooth muscle actin (α-SMA) in both hernial-fascial ring/neck tissue (HRT) and hernia sack tissue (HST) compared to the controls
The H&E staining displayed alterations in tissue architecture, fibroblast morphology, and extracellular matrix (ECM) organization in the IH tissues when compared with controls (Fig. 2)

Summary

Introduction

The incidence of IH following a laparotomy is on average reported to be between 10–20% but is much higher (up to 30%) in certain subpopulations such as those undergoing a colectomy for diverticulitis [1] [2]. The development of an incisional hernia (IH) following a laparotomy is the result of many factors and associated comorbid conditions but inflammation and disorganization of abdominal wall extracellular matrix (ECM) aggravate the pathology and undoubtedly play a significant role [3]. Alterations in connective tissue metabolism especially the collagenopathies has gained significance in IH pathology, as the histology of the IH tissues are characterized by drastic ECM disorganization [3] [5]. The biochemical pathology of IH formation reveals the derangements in the expression of collagen subtypes and dysregulation of matrix metalloproteinases (MMPs). The decreased ratio of collagen I/III and the hyperactivity of various MMPs lead to weak ECM which in turn paves way to IH formation [6]

Methods

Results

Discussion

Conclusion