# Biomechanical drivers of cystogenesis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $662,838

## Abstract

PROJECT SUMMARY
Tubules are characterized by a luminal space surrounded by polarized epithelial cells. Cell
polarization, that is the asymmetric segregation of polarity factors along the axis perpendicular
to the adhesion substrate (apicobasal polarity) or parallel to the epithelial sheet (planar cell
polarity), is required for the directionality of cellular functions and responses, such as absorption
and secretion, cell movement, and proliferation. The maintenance of apical-basal polarity relies
on the integration of mechanobiological signals deriving from cell-cell and cell-extracellular
matrix (ECM) interactions. Derailment of these concerted exchanges leads to tubular
malformations such as tubular dilation, or cystogenesis, and loss of tubule physiological
function, which are pathognomonic of polycystic kidney disease. However, to date, there has
been no experimental or computational studies that describe how biomechanical imbalance
could contribute to cystogenesis. Increasing evidence suggests that mutations in the Pkd1
gene, causative of autosomal dominant polycystic kidney disease, are associated with
abnormalities in the core mechanosensitive machinery of epithelial cells. Our preliminary
findings indicate that the cystogenesis caused by the deletion of Pkd1 or the ciliary Ift88 gene
can be reverted to the normal phenotype by the ablation of integrin-?1, a main ECM receptor.
Based on these observations, we hypothesize that the equilibrium of the biomechanical forces
generated between intercellular junctions and ECM is essential to establish and maintain tubular
integrity. To test this hypothesis, we will use highly integrated theoretical and experimental
assays, including biophysical, cell biological, computational, and in vivo approaches. Our
approach can lead to the identification of novel drug targets that could reverse this
fundamentally unique biophysical disease mechanism. The proposed studies will establish a
comprehensive model of the biophysical mechanisms of renal cystogenesis, and they may
uncover new effector pathways that could be therapeutically targeted.

## Key facts

- **NIH application ID:** 10344339
- **Project number:** 1R01DK131047-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Evren U. AZELOGLU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $662,838
- **Award type:** 1
- **Project period:** 2021-09-24 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10344339

## Citation

> US National Institutes of Health, RePORTER application 10344339, Biomechanical drivers of cystogenesis (1R01DK131047-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10344339. Licensed CC0.

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