Human cystatin C in fibrotic diseases

• Cystatin C is an extracellular tight-binding inhibitor of cysteine cathepsins. • Human cystatin C (hCC) is a relevant marker of glomerular filtration rate (GFR) • hCC is overexpressed during cardiac, lung or liver fibrosis. • hCC could promote matrix deposition by inhibition of proteolytic enzymes. • hCC has been proposed as a potential biomarker of fibrosis. Human cystatin C (hCC), which has a pervasive distribution within body fluids and is ubiquitously expressed by numerous cells and tissues, is a highly potent extracellular inhibitor of cysteine proteases. Besides measurement of serum creatinine, which is the most widely used technique for appraising glomerular filtration rate (GFR), hCC has emerged as a relevant GFR biomarker, because its quantification in serum is less sensitive to interferences with factors such as age, muscle mass or diet. Moreover, there are growing body of evidence that hCC overexpression and/or oversecretion, which is primarily driven by TGF-β1, occur during fibrogenesis (cardiac, liver, oral, and lung fibrosis). Even though molecular mechanisms and signaling pathways governing the regulation of hCC remain to be deciphered more acutely, current data sustain that hCC expression relates to myofibrogenesis and that hCC could be a specific and valuable biomarker of fibrotic disease.