title: Myofibroblasts, regeneration or renal fibrosis--is there a decisive hint?
abstract: Activated fibroblasts, denoted as myofibroblasts, express smooth muscle actin (SMA) and are considered key mediators of renal fibrosis. To identify and isolate these elusive cells, LeBleu et al. generated a new transgenic mouse model expressing a red fluorescent protein under the control of the alpha SMA promoter. Gene expression profiling from cultured myofibroblasts identified human epididymis protein 4 [HE4, also denoted whey acidic protein (WAP) four-disulphide core domain 2] as the most upregulated gene. Since the WAP domains are implicated in protease inhibition, the authors demonstrate the ability of recombinant HE4 to bind and inhibit a number of known proteases. To demonstrate an involvement of HE4 in disease pathology, the authors next showed that the neutralization of HE4 alleviates kidney fibrosis in murine disease models, i.e. 5/6 nephrectomy, unilateral ureteral obstruction and nephrotoxic serum-induced nephritis. Finally, they went on to verify the enhanced expression of HE4 in human fibrosis-associated fibroblasts in comparison to normal fibroblasts as well as in serum samples of patients with chronic kidney diseases. Thus, they conclude that HE4 can serve as a biomarker as well as a therapeutic target for the treatment of renal fibrosis.
authors: Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany.
authors: Jonathan A
authors: JA
authors: Lindquist
authors: Peter R
authors: PR
authors: Mertens
mesh_terms: D000818:Animals; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008297:Male; D011506:Proteins / Q000502:physiology*
chemical_list: D011506:Proteins
keywords: protease inhibitor; renal fibrosis; whey acidic protein (WAP) domain