title: Defects in MAP1S-mediated autophagy turnover of fibronectin cause renal fibrosis.
abstract: Excessive deposition of extracellular matrix proteins in renal tissues causes renal fibrosis and renal function failure. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles. MAP1S is an autophagy activator and promotes the biogenesis and degradation of autophagosomes. Previously, we reported that MAP1S suppresses hepatocellular carcinogenesis in a mouse model and predicts a better prognosis in patients suffering from clear cell renal cell carcinomas. Furthermore, we have characterized that MAP1S enhances the turnover of fibronectin, and mice overexpressing LC3 but with MAP1S deleted accumulate fibronectin and develop liver fibrosis because of the synergistic impact of LC3-induced over-synthesis of fibronectin and MAP1S depletion-caused impairment of fibronectin degradation. Here we show that a suppression of MAP1S in renal cells caused an impairment of autophagy clearance of fibronectin and an activation of pyroptosis. Depletion of MAP1S in mice leads to an accumulation of fibrosis-related proteins and the development of renal fibrosis in aged mice. The levels of MAP1S were dramatically reduced and levels of fibronectin were greatly elevated in renal fibrotic tissues from patients diagnosed as renal atrophy and renal failure. Therefore, MAP1S deficiency may cause the accumulation of fibronectin and the development of renal fibrosis.
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.|Center for the Innovation and Translation of Minimally Invasive Techniques, Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.|Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA.
authors.forename: Guibin
authors.initials: G
authors.lastname: Xu
authors.affiliation: Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Yue
authors.affiliation: Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA.|Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.|Center for the Innovation and Translation of Minimally Invasive Techniques, Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.|Center for the Innovation and Translation of Minimally Invasive Techniques, Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.|Center for the Innovation and Translation of Minimally Invasive Techniques, Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.|Center for the Innovation and Translation of Minimally Invasive Techniques, Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.|Center for the Innovation and Translation of Minimally Invasive Techniques, Guangzhou Medical University, Guangzhou, Guangdong, 510700, China.
authors.forename: Xianhan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA.|Department of Molecular and Cellular Medicine, College of Medicine, Texas A and M Health Science Center, TX 77843, USA.
authors.forename: Leyuan
authors.initials: L
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism*; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D051437:Renal Insufficiency / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D005353:Fibronectins; C570460:MAP1S protein, mouse; D008869:Microtubule-Associated Proteins
keywords: MAP1S; autophagy; caspase 1; collagen; fibronectin; inflammasome; pyroptosis; renal atrophy; renal fibrosis