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The Apoptotic Program Promotes Tissue Remodeling and Fibrosis

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The Apoptotic Program Promotes Tissue Remodeling and Fibrosis View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector letter to the editor The apoptotic program promotes The Authors reply: In their letter, Pallet and He´bert1 tissue remodeling and fibrosis astutely observe that renal cell injury including apoptosis potentially aggravates renal fibrosis, inflammation, and To the Editor: Havasi and Borkan1 discussed recent chronic organ injury. The specific messengers that precipitate observations that link apoptosis to cell deletion and loss of fibrosis and alterations in extracellular matrix proteins are organ function after acute kidney injury. Although the major debated and include chemotactic factors, profibrogenic consequence of apoptosis is cell death, emerging evidence cytokines such as epidermal growth factor and transforming suggests that apoptosis is involved in tissue remodeling and growth factor b, proinflammatory caspases, and cathepsin. In fibrogenesis. addition, it is now accepted that acute kidney injury often The molecular machinery regulating the effector phase of leaves subtle tubular and vascular defects associated with apoptosis favors the extracellular translocation of a highly renal fibrosis and increases the risk of end-stage renal regulated set of mediators of importance in leukocyte disease.2,3 In addition to the above ‘messengers of injury’, trafficking and tissue remodeling. This molecular legacy recent evidence suggests that many cell types are capable of mounts a communication network with surrounding cells to releasing microvesicles containing both RNA and DNA that tissue repair in a paracrine manner, which is of importance in induce signals in other cell types and even in distant tissues in the setting of kidney injury.2 a paracrine/endocrine fashion.4 Although we focused on the Indeed, apoptotic cells release chemotactic factors, acute consequences of renal cell injury and apoptosis in our including fractalkine, monocyte chemoattractant protein 1, review,5 Pallet and He´bert’s letter identifies a key research and lysophosphatidylcholine, to promote the recruitment area, namely, the biological relationship between acute and of macrophages and monocytes at the site of apoptosis.2 chronic kidney injury and the propensity of acute renal Apoptotic cells produce profibrogenic cytokines, including injury to precipitate damage in other organs. Given the epidermal growth factor, and their engulfment by phagocytes recent appreciation that acute injury begets chronic organ promotes transforming growth factor-b secretion. Caspase-3 disease,6 it is essential that we identify the profibrotic activation in apoptotic endothelial cells triggers the export of messengers and their targets to interrupt an epidemic of connective tissue growth factor, which in turn functions as a organ failure. necessary co-factor of myofibroblast differentiation.3 Caspase-3 activation also leads to the externalization of cathepsin L, 1. Pallet N, He´bert M-J. The apoptotic program promotes tissue remodeling which in turn cleaves the extracellular matrix component and fibrosis. Kidney Int 2011; 80: 1108. perlecan generating a truncated C terminal fragment (LG3) 2. Swaminathan S, Shah SV. Novel inflammatory mechanisms of accelerated atherosclerosis in kidney disease. Kidney Int 2011; 80: 453–463. that activates prosurvival pathways in fibroblasts and vascular 3. Pannu N, James M, Hemmelgarn BR, Dong J et al. Modification of smooth muscle cells.4 outcomes after acute kidney injury by the presence of CKD. Am J Kidney Dis 2011; 58: 206–213. In conclusion, apoptosis should be viewed not only as a 4. Reich III CF, Pisetsky DS. The content of DNA and RNA in microparticles cell-deletion pathway but also as a biological process that released by Jurkat and HL-60 cells undergoing in vitro apoptosis. Exp Cell engages intercellular crosstalks of central importance in tissue Res 2009; 315: 760–768. 5. Havasi A, Borkan SC. Apoptosis and acute kidney injury. Kidney Int 2011; remodeling and repair. 80: 29–40. 6. Sanoff S, Okusa MD. Impact of acute kidney injury on chronic kidney 1. Havasi A, Borkan SC. Apoptosis and acute kidney injury. Kidney Int 2011; disease and its progression. Contrib Nephrol 2010; 171: 213–217. 80: 29–40. 2. Cailhier JF, Laplante P, Hebert MJ. Endothelial apoptosis and chronic Andrea Havasi1 and Steven C. Borkan2 transplant vasculopathy: recent results, novel mechanisms. 1Renal Section, Boston University, Boston, Massachusetts, USA and Am J Transplant 2006; 6: 247–253. 2 3. Laplante P, Sirois I, Raymond MA et al. Caspase-3-mediated secretion of Renal Section, Boston Medical Center, Boston, Massachusetts, USA connective tissue growth factor by apoptotic endothelial cells promotes Correspondence: Steven C. Borkan, Renal Section, Boston Medical Center, fibrosis. Cell Death Differ 2010; 17: 291–303. Evan’s Suite 434, 88 East Newton Street, Boston, Massachusetts 02118, USA. 4. Laplante P, Raymond MA, Labelle A et al. Perlecan proteolysis induces an E-mail: [email protected] alpha2beta1 integrin- and Src family kinase-dependent anti-apoptotic pathway in fibroblasts in the absence of focal adhesion kinase activation. Kidney International (2011) 80, 1108; doi:10.1038/ki.2011.309 J Biol Chem 2006; 281: 30383–30392. Nicolas Pallet1 and Marie-Jose´eHe´bert1 Hydrogen sulfide increases after a 1Centre de Recherche de l’Hoˆpital Notre Dame, Centre Hospitalier de l’Universite´ de Montre´al (CRCHUM), Montreal, Quebec, Canada single hemodialysis session Correspondence: Marie-Jose´eHe´bert, Centre de Recherche de l’Hoˆpital Notre Dame, Centre Hospitalier de l’Universite´ de Montreal, 1560 Rue To the Editor: Hydrogen sulfide, H2S, the third endogenous Sherbrooke East, Montre´al, Quebec, Canada H2L 4M1. E-mail: [email protected] gas with cardiovascular properties after nitric oxide and carbon monoxide, is a newly recognized vasorelaxant, and Kidney International (2011) 80, 1108; doi:10.1038/ki.2011.307 H2S deficiency is involved in the pathogenesis of hypertension 1108 Kidney International (2011) 80, 1107–1109.
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