Table 1.
Selected examples of known LOX/LOXL family links with various non-cancerous settings.
| Idiopathic Pulmonary Fibrosis (IPF) | |
| β-aminopropionitrile (BAPN) found to inhibit pulmonary fibrosis in a lung model of silicosis | [34] |
| LOX activity induced in bleomycin-induced lung fibrosis and alleviated by treatment with LOX/LOXL inhibitor | [35,36,37] |
| In IPF patients, elevated serum levels of LOXL2 are associated with an increased risk for disease progression. | [38] |
| LOX activity promotes the progress of EMT in a paraquat model of IPF. | [39,40] |
| A comparative analysis shows that LOX/LOXL2 are elevated in IPF fibroblasts, while LOXL2/3 activity is crucial for fibroblast-to-myofibroblast transition (FMT). | [41] |
| Elevated serum levels of LOXL2 are associated with rheumatoid arthritis -associated interstitial lung disease (RA-ILD). | [42] |
| Increased collagen fibril thickness in IPF versus non-IPF lung tissues is correlated with increased levels of LOXL1/LOXL2 protein, and a decrease in LOX protein expression. | [43] |
| Loss of LOXL1 activity prevents the development of fibrosis in a transforming growth factor-β1-induced model of pulmonary fibrosis. | [44] |
| In bleomycin-induced lung fibrosis, nuclear expression of LOXL2 appears to be a major element in the progression of lung fibrosis. | [45] |
| LOXL2 inhibitor induces collagen turnover in ex vivo lung explants from patients with IPF. | [46] |
| In a study comparing extracellular vesicles (EVs) from IPF-derived pulmonary fibroblast cell lines versus normal pulmonary fibroblast cell lines for differentially expressed proteins, LOXL1 was found in IPF EVs. | [47] |
| Kidney Fibrosis | |
| LOXL2 is expressed in compartments of renal tissue, where it appears to contribute to the progression of tubulointerstitial fibrosis. | [48] |
| LOXL2 inhibition significantly reduced interstitial fibrosis in a mouse model of renal fibrosis. | [49] |
| Elevated serum LOX and LOXL2 levels may act as a potential biomarker for kidney fibrosis. | [50] |
| In a murine model of cyclosporine induced nephropathy, pan-LOX and LOXL2 specific inhibitors attenuated kidney damage. | [51] |
| Liver Fibrosis | |
| Increased LOX levels both in tissue and serum is associated with collagen in the extracellular space in animal models of hepatic fibrosis. | [52,53,54,55] |
| Hepatic stellate cell activation results in elevated LOX mRNA and protein in liver fibrosis. | [56,57,58,59] |
| Lysyl oxidase activity levels increase in patient serum from chronic persistent hepatitis to chronic active hepatitis to cirrhosis. | [60] |
| In a mouse model of liver fibrosis, increased steady state levels of LOXL mRNA occur early in fibrosis development. | [61] |
| Expression of LOX and LOXL2 in hepatocytes is linked to liver fibrosis. | [62] |
| Reduced levels of miR-29b are associated with elevated levels of LOX in models of liver fibrosis. | [63] |
| In patients with severe obesity or obstructive sleep apnoea, serum levels of lysyl oxidase can act as a potential biomarker of liver fibrosis. | [64] |
| Targeting of LOXL2 is associated with anti-fibrotic effects in a mouse model of hepatic fibrosis. | [65] |
| Links between LOXL2, insulin resistance and fibrosis accumulation in non-alcoholic fatty liver disease (NAFLD) are identified. | [66] |
| LOXL1 identified as a candidate therapeutic target for ameliorating liver fibrosis progression in cirrhosis, and inhibition of human hepatic stellate cell mediated fibrogenesis. | [67,68] |
| First demonstration that a small molecule dual inhibitor of LOXL2/3 (PXS-5153A) can ameliorate fibrosis in models of liver fibrosis and myocardial infarct | [69] |
| Patients with HCV who demonstrated sustained responses to antiviral therapy were shown to have regression in liver fibrosis associated with decreased LOXL2 expression. | [70] |
| anti-LOXL2 based therapy in a mouse model of liver fibrosis results in reduced fibrosis via accelerated collagenolytic activity by macrophages. | [71] |
| miR-15b/16 are downregulated in activated hepatic stellate cells (HSCs), and overexpression of these miRs is found to suppress LOXL1 expression in HSCs and induce a fibrogenic response. | [72,73] |
| Selective deletion of LOXL1 in HSCs in a murine NAFLD model ameliorates fibrosis, and serum levels of LOXL1 are positively correlated with histological fibrosis progression in NAFLD patients. | [74] |
| Amyotrophic Lateral Sclerosis (ALS) | |
| LOX transcripts are overexpressed in patient lumbar spinal cord samples. | [75] |
| LOX activity increased in animal model of ALS. | [76] |
| Systemic Sclerosis | |
| LOX mRNA transcripts overexpressed in fibroblasts from patients with systemic sclerosis | [77,78] |
| Elevated levels of LOX found in the serums of patients with systemic sclerosis | [78,79] |
| Elevated levels of LOX and LOXL2 in skin and lungs of systemic sclerosis patients | [37] |
| Elevated serum LOX levels and idiopathic pulmonary arterial hypertension (iPAH) found in patients with systemic sclerosis | [80] |
| LOXL4 activity as a cause of cutaneous fibrosis in fibroblasts from patients with system sclerosis identified | [81] |