Review for 10.1186/1471-230X-2-4 (2002)

Reviewer's□report 
□Evidence□For□Modulation□Of□Pericryptal□Sheath□Myofibroblasts□In□Rat□Descending□Colon□By□ Title: 
Transforming□Growth□Factor□b□And□Angiotensin□II. 
Authors: 
Jay□R□Thiagarajah□( jaythiagarajah@hotmail.com )
Nina□M□Griffiths□( nina.griffiths@ipsn.fr )
kevin□C□pedley□( K.C.Pedley@massey.ac.nz )
Richard□J□Naftalin□( richard.naftalin@kcl.ac.uk@kcl.ac.uk )
□2□ □6□Dec□2001 Version: Date: 
□Dr□Jack□Groot Reviewer: 
□not□specified Level□of□interest: 
□Other□(see□below) Advice□on□publication: 
1.□General□comment.□This□ms□contains□interesting□findings□about□the□effect□of□the□ 
aldosteron-angiotensin□system□(AAS)□on□the□modulation□of□colonic□myofibroblasts□forming□a□pericryptal□ sheath.□This□laboratory□has□earlier□presented□evidence□for□an□absorptive□function□of□the□colonic□crypts□ 
based□on□the□tightness□of□this□sheath,□a□tissue□layer□around□the□crypts□formed□by□myofibroblast.□ 
The□findings□are□of□considerable□scientific□and□medical□interest,□however,□the□presentation□is□such□that□ this□will□not□be□recognised□by□the□unprepared□reader.□ 
2.□Based□on□published□effects□of□high□angiotensin□II□on□fibrotic□tissue□surrounding□arterioles,□the□ 
laboratory□has□already□shown□that□markers□for□myofibroblasts□increase□in□abundance□when□rats□were□ put□on□a□low□sodium□diet□to□increase□the□AAS.□They□now□show□that□low□sodium□induce□an□increase□of□ 
angiotensin□converting□enzyme,□angiotensin□receptors,□TGF-beta□receptors,□which□when□activated□may□ 
trigger□myofribroblasts□to□release□extracellular□matrix□material.□However,□the□direct□relation□between□ these□findings□is□not□given□by□the□experiments□described□in□this□ms.□ 
3.□The□experimental□material□consists□of□fixed□distal□colonic□mucosa□from□Wistar□rats□exposed□to□low□or□ 
high□sodium□diet□or□to□irradiation.□Immunocytochemical□staining□was□analyzed□using□confocal□ microscopy.□Colonic□mucosa□was□compared□with□mucosa□from□the□caecum,□where□crypts□are□not□able□ to□absorb.□A)□Reasoning□for□bringing□together□the□results□from□the□two□experimental□approaches□is□not□ 
given.□B)□It□is□also□not□made□clear□when□sodium□dieting□rats□were□sacrificed□and□why□irradiated□rats□were 
sacrificed□after□1□or□more□months.□Were□they□irradiated□just□once?□What□symptoms□showed□the□rats,□did□ 
they□eat□normal□in□all□groups?□ 
C)□Confocal□images□were□taken□from□5□layers,□analyses□was□done□only□on□two□layers,□explain□why.□ 
D)□Also,□give□the□light/dark□regime□and□state□the□type□of□housing□in□the□diet-experiments.□Also□state□ 
whether□all□animals□were□sacrificed□at□the□same□moment.□Is□the□flour□and□bran□diet□standardized,□state□ 
source.□ 
E)□Captopril□is□used□only□in□the□radiation□experiments.□It□would□be□much□more□illustrative□when□capropril□ 
could□prevent□the□changes□induced□by□low□sodium□diet□in□the□10□day□experiments.□Use□captopril□in□ 
sodium□diet□as□well.□ 
4)□The□writing□does□not□make□it□easy□for□the□reader□to□follow□the□thoughts□of□the□authors.□This□is□the□more 
because□in□a□large□number□of□sentences□words□are□missing□suggesting□that□the□authors□didn't□take□the□ 
time□to□re-read□their□ms□carefully,□also□check□the□references□(e.g.□p□3□last□line).□The□authors□should□also□ give□the□reader□the□necessary□information□e.g.□is□OB□cadherin□increased□per□myofibroblast□or□does□the□ 
increase□indicate□an□increased□number□of□fibroblasts?□Give□these□informations□in□the□beginning□of□the□ 
ms□not□at□the□end.□Also:□if□in□caecum□there□is□no□increase□how□does□this□relates□to□absence□of□pericryptal
barrier□and□unresponsivity□to□low□sodium□(p□11).□There□is□to□much□left□to□the□fantasy□of□the□reader.□ 
5)□The□readability□of□the□ms□should□be□increased□strongly:□e.g.□rewrite□the□introduction□and□make□the□ 
goal□clear□from□the□beginning,□based□on□the□hypothesis□of□the□role□of□the□pericryptal□sheath.□The□ references□to□vascular□tissue□and□other□fibrotic□tissue□should□be□used□as□an□introduction□to□the□idea□to□ increase□the□sheath□by□activating□the□AAS.□Explain□much□clearer□why□you□look□for□all□the□proteins□and□ 
indicate□what□is□new□and□what□is□in□analogy□to□vascular□and□lung□tissue.□Shorten□the□discussion□and□ 
improve□the□order□of□paragraphs.□Explain□much□clearer□why□caecum□differs□and□explain.□Restrict□the□ 
claims□to□the□correlation,□there□is□yet□no□prove□for□the□direct□relation,□accordingly:□change□the□title.□Give□a 
complete□list□of□abbreviations.□ 
Competing□interests: 
None□declared.