title: Erythropoietin ameliorates renal interstitial fibrosis via the inhibition of fibrocyte accumulation.
abstract: Erythropoietin (EPO) is a hematopoietic hormone that protects against renal interstitial fibrosis in animal models; however, the mechanism underlying the anti‑fibrotic activity of EPO has remained elusive. The present study aimed to elucidate this mechanism. Twenty‑four male C57BL6 mice were randomly divided into four groups, each comprising six mice: (i) control group (Sh); (ii) unilateral ureteral obstruction (UUO) plus vehicle group (U+V); (ⅲ) UUO plus 300 U/kg body weight recombinant human (rh)EPO (U+E1) and (ⅳ) UUO plus 1,000 U/kg body weight rhEPO (U+E2). Seven days post‑surgery, the mice were sacrificed for examination. UUO induced significant deposition of extracellular matrix, detected by picro‑sirius red staining, which was decreased following rhEPO treatment. UUO also induced deposition of collagen I and fibronectin, rhEPO treatment was able to attenuate this effect at protein and mRNA levels. Compared with the control groups, UUO resulted in the accumulation of α‑smooth muscle actin‑positive cells in the interstitium, an effect which was ameliorated by rhEPO. Furthermore, rhEPO abrogated the UUO‑induced increase in the number of bone marrow‑derived myofibroblasts. Mechanistically, it was discovered that rhEPO decreased CXC chemokine ligand 16 (CXCL16) expression at protein level. However, treatment with rhEPO did not alter the protein expression of CC chemokine ligand 21 or CXCL12. These results suggested that rhEPO decreased fibrocyte accumulation via the suppression of renal CXCL16, which resulted in the attenuation of renal fibrosis.
authors.affiliation: Department of Urology, Wuhan Central Hospital, Wuhan, Hubei 430014, P.R. China.
authors.forename: Xu Chang
authors.initials: XC
authors.lastname: Geng
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Zhou Pang
authors.initials: ZP
authors.lastname: Hu
authors.affiliation: Department of Urology, Wuhan Central Hospital, Wuhan, Hubei 430014, P.R. China.
authors.forename: Guo Yong
authors.initials: GY
authors.lastname: Lian
mesh_terms: D000818:Animals; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004921:Erythropoietin / Q000494:pharmacology*; D005355:Fibrosis; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D004921:Erythropoietin