Fibrosis
How Does the Body’s Normal Repair Process Go Awry?
Fibroblasts are the most common cell found in connective tissues throughout the body. They secrete collagen proteins that the body uses to create and maintain structural frameworks as needed. During chronic lung injury, the body’s uncontrolled repair process leads to the formation of scar tissue. In diseases like idiopathic pulmonary fibrosis (IPF), the over-formation of scar tissue results in fibrosis, or excessive stiffness in the lungs’ extracellular matrix.
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MMP-7Matrix Metalloproteinase 7Fibrosis
In 2012, Richards et al. published a study that analyzed 92 potential biomarkers in an initial cohort of 140 patients with IPF, followed by validation with an independent cohort of 101 additional patients with IPF. The authors then developed and tested an integrated risk prediction score using a combination of protein markers and patient characteristics.
The authors found that high concentrations of MMP-7 predicted poor overall survival, poor transplant-free survival, and poor progression-free survival in the initial patient cohort. In the independent validation cohort, high concentrations of MMP-7 predicted poor transplant-free survival and poor overall survival.
Why are we studying this?Evidence of Prognostic Value for MMP-7 was found in the following research:Related Clinical Trials
Structured Exercise Training Programme in Idiopathic Pulmonary Fibrosis (Rehab-IPF)
Evaluation of Oral ORIN1001 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
FIBRotic Interstitial Lung Disease and Nocturnal OXygen (FIBRINOX)
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POSTNPeriostinFibrosis
In 2018, Neighbors et al. published a post-hoc analysis of the test and replication cohorts from the CAPACITY 004, CAPACITY 006, and ASCEND phase III clinical trials of pirfenidone. For this analysis, the authors were interested in the predictive and prognostic qualities of 12 biomarkers in IPF, one of which was POSTN. The authors chose POSTN because it is expressed at elevated concentrations in tissue and blood from IPF patients. POSTN is also associated with IPF disease progression.
However, higher baseline POSTN concentrations were associated with larger forced vital capacity (FVC) decline.
Why are we studying this?
Evidence of Prognostic Value for POSTN was found in the following research:
Related Clinical Trials
Cardiovascular Fibrosis in Idiopathic Pulmonary Fibrosis (CardioIPF)
Structured Exercise Training Programme in Idiopathic Pulmonary Fibrosis (Rehab-IPF)
Fibroblast Specific Inhibition of LOXL2 and TGFbeta1 Signaling in Patients With Pulmonary Fibrosis
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TN-CTenascin CFibrosis
TN-C, an extracellular matrix protein expressed during wound healing, has been identified at elevated levels in the lungs of patients with IPF. Van der Velden et al. published a paper in 2016 that tested an experimental JNK inhibitor known as CC-930. Their phase II cohort study of IPF patients measured CC-930’s effect on TN-C levels as an exploratory endpoint.
The mean predicted forced vital capacity (FVC) declined after patients took CC-930 for 26–32 weeks. The authors found that changes in patients’ TN-C levels significantly correlated with changes in predicted FVC. The same was true of patients’ MMP-7 and SP-D levels.
Why are we studying this?
Evidence of Prognostic Value for TN-C was found in the following research:
JNK inhibition reduces lung remodeling and pulmonary fibrotic systemic markers (van der Velden 2016)
Related Clinical Trials