Myriad Functions of Stanniocalcin-1 (STC1) Cover Multiple Therapeutic Targets in the Complicated Pathogenesis of Idiopathic Pulmonary Fibrosis (IPF)

Abstract

Idiopathic pulmonary fibrosis (IPF) is an intractable disease for which the pathological findings are characterized by temporal and spatial heterogeneity. The pathogenesis is composed of myriad factors, including repetitive injuries to epithelial cells, alterations in immunity, the formation of vascular leakage and coagulation, abnormal wound healing, fibrogenesis, and collagen accumulation. Therefore, the molecular target drugs that are used or attempted for treatment or clinical trials may not cover the myriad therapeutic targets of IPF. In addition, the complicated pathogenesis results in a lack of informative biomarkers to diagnose accurately the status of IPF. These facts point out the necessity of using a combination of drugs, that is, each single drug with molecular targets or a single drug with multiple therapeutic targets. In this review, we introduce a humoral factor, stanniocalcin-1 (STC1), which has myriad functions, including the maintenance of calcium homeostasis, the promotion of early wound healing, uncoupling respiration (aerobic glycolysis), reepithelialization in damaged tissues, the inhibition of vascular leakage, and the regulation of macrophage functions to keep epithelial and endothelial homeostasis, which may adequately cover the myriad therapeutic targets of IPF.

A proteomic atlas of senescence-associated secretomes for aging biomarker development

“…Strikingly, one cluster, consisting of just three proteins-chemokine C-X-C motif ligand 1 (CXCL1), MMP1, and stanniocalcin 1 (STC1)-were highly represented in the sSASPs of all inducers, suggesting these proteins might serve as surrogate markers of the sSASP. Of note, STC1, among the top sSASP proteins, is a previously unidentified SASP factor and a secreted hormone with many disease associations [35][36][37][38][39][40]. Our analyses also validate MMP1 and CXCL1 as SASP markers.…”

“…Additionally, two of the top core sSASP proteins identified by an unbiased k-means clustering algorithm-STC1 and MMP1 (Fig 7B and 7C)-were reported as significant aging biomarkers [48]. In addition to aging, MMP1 has been identified as a biomarker for several cancers, pulmonary fibrosis, and potentially Alzheimer's disease [68][69][70][71], whereas STC1 has been identified as a diagnostic and prognostic biomarker for cancers, pulmonary fibrosis, renal ischemia/reperfusion injury, and Alzheimer's disease [35][36][37][38][39][40].…”

Plasma proteomic biomarker signature of age predicts health and life span

“…Several other top SASP components that we identified in plasma are also previously reported health biomarkers ( Basisty et al, 2020 ). In addition to aging, MMP1 is a biomarker for several cancers, pulmonary fibrosis and potentially Alzheimer’s disease ( Bhat et al, 2012 ; Chen et al, 2016b ; Rosas et al, 2008 ), whereas STC1 is a diagnostic and prognostic biomarker for cancers, pulmonary fibrosis, renal ischemia/reperfusion injury and Alzheimer’s disease ( Chang et al, 2015 ; Ohkouchi et al, 2015 ; Pan et al, 2015 ; Shahim et al, 2017 ).…”

A looming role of mitochondrial calcium in dictating the lung epithelial integrity and pathophysiology of lung diseases

“…Thus, mitochondrial calcium influx and MCU can be a therapeutic target in IPF ( Gu et al, 2019 ). Mitochondrial hormone Stanniocalcin 1 which regulates calcium homeostasis also has a role in the secretion of transforming growth factor beta and can be a therapeutic target in IPF ( Ohkouchi et al, 2015 ).…”